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                <filerCredentials>
                    <cik>0001782817</cik>
                    <ccc>XXXXXXXX</ccc>
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            <liveTestFlag>LIVE</liveTestFlag>



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        <issuerInfo>
            <issuerCik>0001701108</issuerCik>
            <issuerName>SPERO THERAPEUTICS, INC.</issuerName>
            <secFileNumber>001-38266</secFileNumber>
            <issuerAddress>
                <ns2:street1>675 Massachusetts Avenue, 14th  Floor</ns2:street1>
                <ns2:city>Cambridge</ns2:city>
                <ns2:stateOrCountry>MA</ns2:stateOrCountry>
                <ns2:zipCode>02139</ns2:zipCode>
            </issuerAddress>
            <issuerContactPhone>(857) 242-1600</issuerContactPhone>
            <nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>SATYAVRAT SHUKLA</nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>
            <relationshipsToIssuer>
                <relationshipToIssuer>Officer</relationshipToIssuer>
            </relationshipsToIssuer>
        </issuerInfo>
        <securitiesInformation>
            <securitiesClassTitle>Common</securitiesClassTitle>
            <brokerOrMarketmakerDetails>
                <name>E*TRADE FINANCIAL CORPORATION</name>
                <address>
                    <ns2:street1>3 EDISON DRIVE</ns2:street1>
                    <ns2:city>ALPHARETTA</ns2:city>
                    <ns2:stateOrCountry>GA</ns2:stateOrCountry>
                    <ns2:zipCode>30005</ns2:zipCode>
                </address>
            </brokerOrMarketmakerDetails>
            <noOfUnitsSold>4163</noOfUnitsSold>
            <aggregateMarketValue>5411.90</aggregateMarketValue>
            <noOfUnitsOutstanding>52696289</noOfUnitsOutstanding>
            <approxSaleDate>08/29/2023</approxSaleDate>
            <securitiesExchangeName>NASDAQ</securitiesExchangeName>
        </securitiesInformation>
        <securitiesToBeSold>
            <securitiesClassTitle>COMMON</securitiesClassTitle>
            <acquiredDate>08/26/2023</acquiredDate>
            <natureOfAcquisitionTransaction>Restricted Stock</natureOfAcquisitionTransaction>
            <nameOfPersonfromWhomAcquired>ISSUER</nameOfPersonfromWhomAcquired>
            <isGiftTransaction>N</isGiftTransaction>
            <amountOfSecuritiesAcquired>4163</amountOfSecuritiesAcquired>
            <paymentDate>08/26/2023</paymentDate>
            <natureOfPayment>Not Applicable</natureOfPayment>
        </securitiesToBeSold>
        <nothingToReportFlagOnSecuritiesSoldInPast3Months>N</nothingToReportFlagOnSecuritiesSoldInPast3Months>
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            <sellerDetails>
                <name>SATYAVRAT SHUKLA</name>
                <address>
                    <ns2:street1>675 Massachusetts Avenue, 14th  Floor</ns2:street1>
                    <ns2:city>Cambridge</ns2:city>
                    <ns2:stateOrCountry>MA</ns2:stateOrCountry>
                    <ns2:zipCode>02139</ns2:zipCode>
                </address>
            </sellerDetails>
            <securitiesClassTitle>common</securitiesClassTitle>
            <saleDate>08/28/2023</saleDate>
            <amountOfSecuritiesSold>1854</amountOfSecuritiesSold>
            <grossProceeds>2261.00</grossProceeds>
        </securitiesSoldInPast3Months>
        <noticeSignature>
            <noticeDate>08/29/2023</noticeDate>
            <planAdoptionDates>
                <planAdoptionDate>05/24/2023</planAdoptionDate>
            </planAdoptionDates>
            <signature>/s/ Satyavrat Shukla</signature>
        </noticeSignature>
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144
0001782817
XXXXXXXX
LIVE
0001701108
SPERO THERAPEUTICS, INC.
001-38266
675 Massachusetts Avenue, 14th  Floor
Cambridge
MA
02139
(857) 242-1600
SATYAVRAT SHUKLA
Officer
Common
E*TRADE FINANCIAL CORPORATION
3 EDISON DRIVE
ALPHARETTA
GA
30005
4163
5411.90
52696289
08/29/2023
NASDAQ
COMMON
08/26/2023
Restricted Stock
ISSUER
N
4163
08/26/2023
Not Applicable
N
SATYAVRAT SHUKLA
675 Massachusetts Avenue, 14th  Floor
Cambridge
MA
02139
common
08/28/2023
1854
2261.00
08/29/2023
05/24/2023
/s/ Satyavrat Shukla