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Oral preexposure prophylaxis (PrEP) has been established as a pivotal strategy in HIV prevention. However, bacterial sexually transmitted infections (STIs), such as Chlamydia trachomatis and Neisseria gonorrhoeae, are also highly prevalent. Although the presence of STI-related mucosal lesions is a known risk factor for HIV acquisition, the potential increase in risk associated with asymptomatic STIs is not completely understood. Recent data demonstrated higher T-cell activation is a risk factor for sexually acquired HIV-1 infection. We examined the effect of asymptomatic C. trachomatis and N. gonorrhoeae anorectal infection on systemic immune activation, potentially increasing the risk of HIV acquisition.We analyzed samples from participants of PrEP Brasil, a demonstration study of daily oral emtricitabine/tenofovir disoproxil fumarate HIV PrEP among healthy MSM, for T-cell activation by flow cytometry. We included 34 asymptomatic participants with anorectal swab for C. trachomatis and/or N. gonorrhoeae infection, whereas negative for other STIs, and 35 controls.We found a higher frequency of human leukocyte antigen DR+CD38+ CD8+ T cells (1.5 vs. 0.9%, P < 0.005) and with memory phenotype in the group with asymptomatic C. trachomatis and/or N. gonorrhoeae infection. Exhaustion and senescence markers were also significant higher in this group. No difference was observed in the soluble CD14 levels.Our findings suggest asymptomatic anorectal C. trachomatis and/or N. gonorrhoeae increase systemic immune activation, potentially increasing the risk of HIV acquisition. Regular screening and treatment of asymptomatic STIs should be explored as adjuvant tools for HIV prevention.