<?xml version="1.0" encoding="UTF-8"?><edgarSubmission xmlns="http://www.sec.gov/edgar/ownership" xmlns:com="http://www.sec.gov/edgar/common">
  <headerData>
    <submissionType>144</submissionType>
    <filerInfo>
      <filer>
        <filerCredentials>
          <cik>0001388325</cik>
          <ccc>XXXXXXXX</ccc>
        </filerCredentials>
      </filer>
      <liveTestFlag>LIVE</liveTestFlag>



    </filerInfo>
  </headerData>
  <formData>
    <issuerInfo>
      <issuerCik>0001683553</issuerCik>
      <issuerName>SPRUCE BIOSCIENCES, INC.</issuerName>
      <secFileNumber>001-39594</secFileNumber>
      <issuerAddress>
        <com:street1>611 GATEWAY BOULEVARD, SUITE 740</com:street1>
        <com:city>SOUTH SAN FRANCISCO</com:city>
        <com:stateOrCountry>CA</com:stateOrCountry>
        <com:zipCode>94080</com:zipCode>
      </issuerAddress>
      <issuerContactPhone>(415) 655-4168</issuerContactPhone>
      <nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>Novo Holdings A/S</nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>
      <relationshipsToIssuer>
        <relationshipToIssuer>10% Stockholder</relationshipToIssuer>
      </relationshipsToIssuer>
    </issuerInfo>
    <securitiesInformation>
      <securitiesClassTitle>Common Stock</securitiesClassTitle>
      <brokerOrMarketmakerDetails>
        <name>Morgan Stanley &amp; Co. LLC</name>
        <address>
          <com:street1>1585 Broadway</com:street1>
          <com:city>New York</com:city>
          <com:stateOrCountry>NY</com:stateOrCountry>
          <com:zipCode>10036</com:zipCode>
        </address>
      </brokerOrMarketmakerDetails>
      <noOfUnitsSold>1912316</noOfUnitsSold>
      <aggregateMarketValue>9485087.36</aggregateMarketValue>
      <noOfUnitsOutstanding>41029832</noOfUnitsOutstanding>
      <approxSaleDate>03/14/2024</approxSaleDate>
      <securitiesExchangeName>NASDAQGS</securitiesExchangeName>
    </securitiesInformation>
    <securitiesToBeSold>
      <securitiesClassTitle>Common Stock</securitiesClassTitle>
      <acquiredDate>10/14/2020</acquiredDate>
      <natureOfAcquisitionTransaction>Conversion of Series A Preferred Stock in Initial Public Offering</natureOfAcquisitionTransaction>
      <nameOfPersonfromWhomAcquired>Spruce Biosciences, Inc.</nameOfPersonfromWhomAcquired>
      <isGiftTransaction>N</isGiftTransaction>
      <amountOfSecuritiesAcquired>3210518</amountOfSecuritiesAcquired>
      <paymentDate>10/14/2020</paymentDate>
      <natureOfPayment>Conversion of Preferred Stock</natureOfPayment>
    </securitiesToBeSold>
    <nothingToReportFlagOnSecuritiesSoldInPast3Months>Y</nothingToReportFlagOnSecuritiesSoldInPast3Months>
    <noticeSignature>
      <noticeDate>03/14/2024</noticeDate>
      <signature>/s/ Barbara Fiorini Due, General Counsel, Finance &amp; Operations</signature>
    </noticeSignature>
  </formData>
</edgarSubmission>
