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Urinary tract infections (UTIs) are common human infections that compromise women's health around the world, even though they can affect men and women of all ages. Bacterial species are the primary causative agents of UTIs, while Staphylococcus saprophyticus, a gram-positive bacterium, is especially important for uncomplicated infections in young women. Despite the number of antigenic proteins identified in Staphylococcus aureus and other bacteria of the genus, there is no immunoproteomic study in S. saprophyticus. In this context, since pathogenic microorganisms secrete important proteins that interact with hosts during infection, the present work aims to identify the exoantigens from S. saprophyticus ATCC 15305 by immunoproteomic and immunoinformatic approaches. We identified 32 antigens on the exoproteome of S. saprophyticus ATCC 15305 by immunoinformatic tools. By using 2D-IB immunoproteomic analysis, it was possible to identify 3 antigenic proteins: transglycosylase IsaA, enolase and the secretory antigen Q49ZL8. In addition, 5 antigenic proteins were detected by immunoprecipitation (IP) approach, where the most abundant were bifunctional autolysin and transglycosylase IsaA proteins. The transglycosylase IsaA was the only protein detected by all the tools approaches used in this study. In this work it was possible to describe a total of 36 S. saprophyticus exoantigens. Immunoinformatic analysis allowed the identification of 5 exclusive linear B cell epitopes from S. saprophyticus and 5 epitopes presenting homology with other bacteria that cause UTIs. This work describes, for the first time, the profile of exoantigens secreted by S. saprophyticus and can contribute to the identification of new diagnostic targets of UTIs, as well as to develop vaccines and immunotherapies against bacterial urinary infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)