<?xml version="1.0" encoding="us-ascii"?>
<!-- DFIN ActiveDisclosure(SM) XBRL Linkbase Document - http://www.dfinsolutions.com/ -->
<!-- Creation Date      : 2021-08-09T15:03:11.9314838+00:00 -->
<!-- Version            : 5.0.1.648 -->
<!-- Package ID         : 34a512b5ea344504ab48eb6493baa49b -->
<!-- Copyright (c) 2021 Donnelley Financial Solutions, Inc. All Rights Reserved. -->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:roleRef xlink:type="simple" xlink:href="sprb-20210630.xsd#TemplateLink" roleURI="http://www.sprucebiosciences.com/20210630/role/TemplateLink" />
  <link:roleRef roleURI="http://www.sprucebiosciences.com/20210630/taxonomy/role/StatementCONDENSEDBALANCESHEETS" xlink:href="sprb-20210630.xsd#Role_StatementCONDENSEDBALANCESHEETS" xlink:type="simple" />
  <link:calculationLink xlink:type="extended" xlink:role="http://www.sprucebiosciences.com/20210630/taxonomy/role/StatementCONDENSEDBALANCESHEETS">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherAssetsCurrent" xlink:type="locator" xlink:label="us-gaap_OtherAssetsCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PrepaidExpenseCurrent" xlink:type="locator" xlink:label="us-gaap_PrepaidExpenseCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShortTermInvestments" xlink:type="locator" xlink:label="us-gaap_ShortTermInvestments" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:type="locator" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherAssetsNoncurrent" xlink:type="locator" xlink:label="us-gaap_OtherAssetsNoncurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermInvestments" xlink:type="locator" xlink:label="us-gaap_LongTermInvestments" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAsset" xlink:type="locator" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RestrictedCashNoncurrent" xlink:type="locator" xlink:label="us-gaap_RestrictedCashNoncurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AssetsCurrent" xlink:type="locator" xlink:label="us-gaap_AssetsCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Assets" xlink:type="locator" xlink:label="us-gaap_Assets" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccruedEmployeeBenefitsCurrent" xlink:type="locator" xlink:label="us-gaap_AccruedEmployeeBenefitsCurrent" />
    <link:loc xlink:href="sprb-20210630.xsd#sprb_AccruedLiabilitiesAndOtherLiabilitiesCurrent" xlink:type="locator" xlink:label="sprb_AccruedLiabilitiesAndOtherLiabilitiesCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebtCurrent" xlink:type="locator" xlink:label="us-gaap_LongTermDebtCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccountsPayableCurrent" xlink:type="locator" xlink:label="us-gaap_AccountsPayableCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherLiabilitiesNoncurrent" xlink:type="locator" xlink:label="us-gaap_OtherLiabilitiesNoncurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent" xlink:type="locator" xlink:label="us-gaap_OperatingLeaseLiabilityNoncurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebtNoncurrent" xlink:type="locator" xlink:label="us-gaap_LongTermDebtNoncurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:type="locator" xlink:label="us-gaap_LiabilitiesCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:type="locator" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:type="locator" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AdditionalPaidInCapitalCommonStock" xlink:type="locator" xlink:label="us-gaap_AdditionalPaidInCapitalCommonStock" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CommonStockValue" xlink:type="locator" xlink:label="us-gaap_CommonStockValue" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PreferredStockValue" xlink:type="locator" xlink:label="us-gaap_PreferredStockValue" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CommitmentsAndContingencies" xlink:type="locator" xlink:label="us-gaap_CommitmentsAndContingencies" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_StockholdersEquity" xlink:type="locator" xlink:label="us-gaap_StockholdersEquity" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_Liabilities" xlink:type="locator" xlink:label="us-gaap_Liabilities" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:type="locator" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_Liabilities" order="10010.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_StockholdersEquity" order="10020.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity" xlink:to="us-gaap_CommitmentsAndContingencies" order="10030.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity" xlink:to="us-gaap_PreferredStockValue" order="10040.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity" xlink:to="us-gaap_CommonStockValue" order="10050.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity" xlink:to="us-gaap_AdditionalPaidInCapitalCommonStock" order="10060.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" order="10070.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit" order="10080.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities" xlink:to="us-gaap_LiabilitiesCurrent" order="10090.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities" xlink:to="us-gaap_LongTermDebtNoncurrent" order="10100.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities" xlink:to="us-gaap_OperatingLeaseLiabilityNoncurrent" order="10110.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities" xlink:to="us-gaap_OtherLiabilitiesNoncurrent" order="10120.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent" xlink:to="us-gaap_AccountsPayableCurrent" order="10130.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent" xlink:to="us-gaap_LongTermDebtCurrent" order="10140.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent" xlink:to="sprb_AccruedLiabilitiesAndOtherLiabilitiesCurrent" order="10150.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent" xlink:to="us-gaap_AccruedEmployeeBenefitsCurrent" order="10160.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_AssetsCurrent" order="10170.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_RestrictedCashNoncurrent" order="10180.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_OperatingLeaseRightOfUseAsset" order="10190.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_LongTermInvestments" order="10200.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_OtherAssetsNoncurrent" order="10210.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue" order="10220.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent" xlink:to="us-gaap_ShortTermInvestments" order="10230.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent" xlink:to="us-gaap_PrepaidExpenseCurrent" order="10240.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent" xlink:to="us-gaap_OtherAssetsCurrent" order="10250.00" priority="2" use="optional" weight="1.00" />
  </link:calculationLink>
  <link:roleRef roleURI="http://www.sprucebiosciences.com/20210630/taxonomy/role/StatementCONDENSEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSSUnaudited" xlink:href="sprb-20210630.xsd#Role_StatementCONDENSEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSSUnaudited" xlink:type="simple" />
  <link:calculationLink xlink:type="extended" xlink:role="http://www.sprucebiosciences.com/20210630/taxonomy/role/StatementCONDENSEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSSUnaudited">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_GeneralAndAdministrativeExpense" xlink:type="locator" xlink:label="us-gaap_GeneralAndAdministrativeExpense" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ResearchAndDevelopmentExpense" xlink:type="locator" xlink:label="us-gaap_ResearchAndDevelopmentExpense" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingExpenses" xlink:type="locator" xlink:label="us-gaap_OperatingExpenses" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:type="locator" xlink:label="us-gaap_OtherNonoperatingIncomeExpense" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_InterestExpense" xlink:type="locator" xlink:label="us-gaap_InterestExpense" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingIncomeLoss" xlink:type="locator" xlink:label="us-gaap_OperatingIncomeLoss" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax" xlink:type="locator" xlink:label="us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetIncomeLoss" xlink:type="locator" xlink:label="us-gaap_NetIncomeLoss" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:type="locator" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_NetIncomeLoss" order="10010.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax" order="10020.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss" xlink:to="us-gaap_OperatingIncomeLoss" order="10030.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss" xlink:to="us-gaap_InterestExpense" order="10040.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss" xlink:to="us-gaap_OtherNonoperatingIncomeExpense" order="10050.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses" xlink:to="us-gaap_ResearchAndDevelopmentExpense" order="10060.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses" xlink:to="us-gaap_GeneralAndAdministrativeExpense" order="10070.00" priority="2" use="optional" weight="1.00" />
  </link:calculationLink>
  <link:roleRef roleURI="http://www.sprucebiosciences.com/20210630/taxonomy/role/StatementCONDENSEDSTATEMENTSOFCASHFLOWSUnaudited" xlink:href="sprb-20210630.xsd#Role_StatementCONDENSEDSTATEMENTSOFCASHFLOWSUnaudited" xlink:type="simple" />
  <link:calculationLink xlink:type="extended" xlink:role="http://www.sprucebiosciences.com/20210630/taxonomy/role/StatementCONDENSEDSTATEMENTSOFCASHFLOWSUnaudited">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInOtherOperatingLiabilities" xlink:type="locator" xlink:label="us-gaap_IncreaseDecreaseInOtherOperatingLiabilities" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInOtherOperatingAssets" xlink:type="locator" xlink:label="us-gaap_IncreaseDecreaseInOtherOperatingAssets" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInEmployeeRelatedLiabilities" xlink:type="locator" xlink:label="us-gaap_IncreaseDecreaseInEmployeeRelatedLiabilities" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsPayableAndAccruedLiabilities" xlink:type="locator" xlink:label="us-gaap_IncreaseDecreaseInAccountsPayableAndAccruedLiabilities" />
    <link:loc xlink:href="sprb-20210630.xsd#sprb_IncreaseDecreaseInPrepaidExpensesAndOtherCurrentAssets" xlink:type="locator" xlink:label="sprb_IncreaseDecreaseInPrepaidExpensesAndOtherCurrentAssets" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:type="locator" xlink:label="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" />
    <link:loc xlink:href="sprb-20210630.xsd#sprb_AmortizationOfPremiumOnAvailableForSaleSecurities" xlink:type="locator" xlink:label="sprb_AmortizationOfPremiumOnAvailableForSaleSecurities" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DepreciationDepletionAndAmortization" xlink:type="locator" xlink:label="us-gaap_DepreciationDepletionAndAmortization" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ShareBasedCompensation" xlink:type="locator" xlink:label="us-gaap_ShareBasedCompensation" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProfitLoss" xlink:type="locator" xlink:label="us-gaap_ProfitLoss" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsToAcquireInvestments" xlink:type="locator" xlink:label="us-gaap_PaymentsToAcquireInvestments" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:type="locator" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RepaymentsOfLongTermDebt" xlink:type="locator" xlink:label="us-gaap_RepaymentsOfLongTermDebt" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProceedsFromIssuanceOfLongTermDebt" xlink:type="locator" xlink:label="us-gaap_ProceedsFromIssuanceOfLongTermDebt" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProceedsFromStockPlans" xlink:type="locator" xlink:label="us-gaap_ProceedsFromStockPlans" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProceedsFromStockOptionsExercised" xlink:type="locator" xlink:label="us-gaap_ProceedsFromStockOptionsExercised" />
    <link:loc xlink:href="sprb-20210630.xsd#sprb_PaymentsOfDeferredOfferingCosts" xlink:type="locator" xlink:label="sprb_PaymentsOfDeferredOfferingCosts" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_ProceedsFromIssuanceOfRedeemableConvertiblePreferredStock" xlink:type="locator" xlink:label="us-gaap_ProceedsFromIssuanceOfRedeemableConvertiblePreferredStock" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:type="locator" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:type="locator" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:type="locator" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:type="locator" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities" order="10010.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities" order="10020.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities" order="10030.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_ProceedsFromIssuanceOfRedeemableConvertiblePreferredStock" order="10040.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:to="sprb_PaymentsOfDeferredOfferingCosts" order="10050.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_ProceedsFromStockOptionsExercised" order="10060.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_ProceedsFromStockPlans" order="10070.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_ProceedsFromIssuanceOfLongTermDebt" order="10080.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:to="us-gaap_RepaymentsOfLongTermDebt" order="10090.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" order="10100.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:to="us-gaap_PaymentsToAcquireInvestments" order="10110.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_ProfitLoss" order="10120.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_ShareBasedCompensation" order="10130.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_DepreciationDepletionAndAmortization" order="10140.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="sprb_AmortizationOfPremiumOnAvailableForSaleSecurities" order="10150.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" order="10160.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="sprb_IncreaseDecreaseInPrepaidExpensesAndOtherCurrentAssets" order="10170.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_IncreaseDecreaseInAccountsPayableAndAccruedLiabilities" order="10180.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_IncreaseDecreaseInEmployeeRelatedLiabilities" order="10190.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_IncreaseDecreaseInOtherOperatingAssets" order="10200.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:to="us-gaap_IncreaseDecreaseInOtherOperatingLiabilities" order="10210.00" priority="2" use="optional" weight="1.00" />
  </link:calculationLink>
  <link:roleRef roleURI="http://www.sprucebiosciences.com/20210630/taxonomy/role/DisclosureSummaryOfSignificantAccountingPoliciesScheduleOfReconciliationOfCashCashEquivalentsAndRestrictedCashDetails" xlink:href="sprb-20210630.xsd#Role_DisclosureSummaryOfSignificantAccountingPoliciesScheduleOfReconciliationOfCashCashEquivalentsAndRestrictedCashDetails" xlink:type="simple" />
  <link:calculationLink xlink:type="extended" xlink:role="http://www.sprucebiosciences.com/20210630/taxonomy/role/DisclosureSummaryOfSignificantAccountingPoliciesScheduleOfReconciliationOfCashCashEquivalentsAndRestrictedCashDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_RestrictedCash" xlink:type="locator" xlink:label="us-gaap_RestrictedCash" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:type="locator" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:type="locator" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue" order="10010.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents" xlink:to="us-gaap_RestrictedCash" order="10020.00" priority="2" use="optional" weight="1.00" />
  </link:calculationLink>
  <link:roleRef roleURI="http://www.sprucebiosciences.com/20210630/taxonomy/role/DisclosureCashEquivalentsAndInvestmentsSummaryOfAmortizedCostUnrealizedGainsAndLossesAndFairValueDetails" xlink:href="sprb-20210630.xsd#Role_DisclosureCashEquivalentsAndInvestmentsSummaryOfAmortizedCostUnrealizedGainsAndLossesAndFairValueDetails" xlink:type="simple" />
  <link:calculationLink xlink:type="extended" xlink:role="http://www.sprucebiosciences.com/20210630/taxonomy/role/DisclosureCashEquivalentsAndInvestmentsSummaryOfAmortizedCostUnrealizedGainsAndLossesAndFairValueDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:type="locator" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure" xlink:type="locator" xlink:label="us-gaap_CashAndCashEquivalentsFairValueDisclosure" />
    <link:loc xlink:href="sprb-20210630.xsd#sprb_CashAndCashEquivalentsGrossUnrealizedLoss" xlink:type="locator" xlink:label="sprb_CashAndCashEquivalentsGrossUnrealizedLoss" />
    <link:loc xlink:href="sprb-20210630.xsd#sprb_CashAndCashEquivalentsGrossUnrealizedGain" xlink:type="locator" xlink:label="sprb_CashAndCashEquivalentsGrossUnrealizedGain" />
    <link:loc xlink:href="sprb-20210630.xsd#sprb_CashAndCashEquivalentsAmortizedCost" xlink:type="locator" xlink:label="sprb_CashAndCashEquivalentsAmortizedCost" />
    <link:loc xlink:href="sprb-20210630.xsd#sprb_CashAndCashEquivalentsAndAvailableForSaleFairValue" xlink:type="locator" xlink:label="sprb_CashAndCashEquivalentsAndAvailableForSaleFairValue" />
    <link:loc xlink:href="sprb-20210630.xsd#sprb_CashAndCashEquivalentsAndAvailableForSaleGrossUnrealizedLoss" xlink:type="locator" xlink:label="sprb_CashAndCashEquivalentsAndAvailableForSaleGrossUnrealizedLoss" />
    <link:loc xlink:href="sprb-20210630.xsd#sprb_CashAndCashEquivalentsAndAvailableForSaleGrossUnrealizedGain" xlink:type="locator" xlink:label="sprb_CashAndCashEquivalentsAndAvailableForSaleGrossUnrealizedGain" />
    <link:loc xlink:href="sprb-20210630.xsd#sprb_CashAndCashEquivalentsAndAvailableForSaleAmortizedCost" xlink:type="locator" xlink:label="sprb_CashAndCashEquivalentsAndAvailableForSaleAmortizedCost" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="sprb_CashAndCashEquivalentsAndAvailableForSaleAmortizedCost" xlink:to="sprb_CashAndCashEquivalentsAndAvailableForSaleGrossUnrealizedGain" order="10010.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="sprb_CashAndCashEquivalentsAndAvailableForSaleAmortizedCost" xlink:to="sprb_CashAndCashEquivalentsAndAvailableForSaleGrossUnrealizedLoss" order="10020.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="sprb_CashAndCashEquivalentsAndAvailableForSaleAmortizedCost" xlink:to="sprb_CashAndCashEquivalentsAndAvailableForSaleFairValue" order="10030.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="sprb_CashAndCashEquivalentsAmortizedCost" xlink:to="sprb_CashAndCashEquivalentsGrossUnrealizedGain" order="10040.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="sprb_CashAndCashEquivalentsAmortizedCost" xlink:to="sprb_CashAndCashEquivalentsGrossUnrealizedLoss" order="10050.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="sprb_CashAndCashEquivalentsAmortizedCost" xlink:to="us-gaap_CashAndCashEquivalentsFairValueDisclosure" order="10060.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" order="10070.00" priority="2" use="optional" weight="-1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" order="10080.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities" order="10090.00" priority="2" use="optional" weight="1.00" />
  </link:calculationLink>
  <link:roleRef roleURI="http://www.sprucebiosciences.com/20210630/taxonomy/role/DisclosureBalanceSheetComponentsScheduleOfAccruedExpensesAndOtherCurrentLiabilitiesDetails" xlink:href="sprb-20210630.xsd#Role_DisclosureBalanceSheetComponentsScheduleOfAccruedExpensesAndOtherCurrentLiabilitiesDetails" xlink:type="simple" />
  <link:calculationLink xlink:type="extended" xlink:role="http://www.sprucebiosciences.com/20210630/taxonomy/role/DisclosureBalanceSheetComponentsScheduleOfAccruedExpensesAndOtherCurrentLiabilitiesDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:type="locator" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent" />
    <link:loc xlink:href="sprb-20210630.xsd#sprb_AccruedGeneralAndAdministrativeExpenses" xlink:type="locator" xlink:label="sprb_AccruedGeneralAndAdministrativeExpenses" />
    <link:loc xlink:href="sprb-20210630.xsd#sprb_AccruedResearchAndDevelopmentExpenses" xlink:type="locator" xlink:label="sprb_AccruedResearchAndDevelopmentExpenses" />
    <link:loc xlink:href="sprb-20210630.xsd#sprb_AccruedLiabilitiesAndOtherLiabilitiesCurrent" xlink:type="locator" xlink:label="sprb_AccruedLiabilitiesAndOtherLiabilitiesCurrent" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="sprb_AccruedLiabilitiesAndOtherLiabilitiesCurrent" xlink:to="sprb_AccruedResearchAndDevelopmentExpenses" order="10010.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="sprb_AccruedLiabilitiesAndOtherLiabilitiesCurrent" xlink:to="sprb_AccruedGeneralAndAdministrativeExpenses" order="10020.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="sprb_AccruedLiabilitiesAndOtherLiabilitiesCurrent" xlink:to="us-gaap_OperatingLeaseLiabilityCurrent" order="10030.00" priority="2" use="optional" weight="1.00" />
  </link:calculationLink>
  <link:roleRef roleURI="http://www.sprucebiosciences.com/20210630/taxonomy/role/DisclosureTermLoanScheduleOfTermLoanDetails" xlink:href="sprb-20210630.xsd#Role_DisclosureTermLoanScheduleOfTermLoanDetails" xlink:type="simple" />
  <link:calculationLink xlink:type="extended" xlink:role="http://www.sprucebiosciences.com/20210630/taxonomy/role/DisclosureTermLoanScheduleOfTermLoanDetails">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet" xlink:type="locator" xlink:label="us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_DebtInstrumentCarryingAmount" xlink:type="locator" xlink:label="us-gaap_DebtInstrumentCarryingAmount" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebt" xlink:type="locator" xlink:label="us-gaap_LongTermDebt" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_DebtInstrumentCarryingAmount" order="10010.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet" order="10020.00" priority="2" use="optional" weight="-1.00" />
  </link:calculationLink>
  <link:roleRef roleURI="http://www.sprucebiosciences.com/20210630/taxonomy/role/DisclosureTermLoanScheduleOfTermLoanDetails2" xlink:href="sprb-20210630.xsd#Role_DisclosureTermLoanScheduleOfTermLoanDetails2" xlink:type="simple" />
  <link:calculationLink xlink:type="extended" xlink:role="http://www.sprucebiosciences.com/20210630/taxonomy/role/DisclosureTermLoanScheduleOfTermLoanDetails2">
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebtNoncurrent" xlink:type="locator" xlink:label="us-gaap_LongTermDebtNoncurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebtCurrent" xlink:type="locator" xlink:label="us-gaap_LongTermDebtCurrent" />
    <link:loc xlink:href="http://xbrl.fasb.org/us-gaap/2020/elts/us-gaap-2020-01-31.xsd#us-gaap_LongTermDebt" xlink:type="locator" xlink:label="us-gaap_LongTermDebt" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_LongTermDebtCurrent" order="10010.00" priority="2" use="optional" weight="1.00" />
    <link:calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_LongTermDebtNoncurrent" order="10020.00" priority="2" use="optional" weight="1.00" />
  </link:calculationLink>
</link:linkbase>
