Background: Oral pre-exposure prophylaxis (PrEP) has been established as a pivotal strategy in HIV prevention. However, bacterial sexually transmitted infections (STIs), such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), 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 CT and NG anorectal infection on systemic immune activation, potentially increasing the risk of HIV acquisition. Methods: We analyzed samples from participants of PrEP Brasil, a demonstration study of daily oral emtricitabine/tenofovir disoproxil fumarate HIV PrEP among healthy men who have sex with men, for T cell activation by flow cytometry. We included 34 asymptomatic participants with anorectal swab for CT and/or NG infectiion while negative for other STIs, and 35 controls. Results: We found a higher frequency of HLA-DR+CD38+ CD8+ T cells (1.5 vs. 0.9% p<0.005) and with memory phenotype in the group with asymptomatic CT and/or NG infection. Exhaustion and senescence markers were also significant higher in this group. No difference was observed in the soluble CD14 levels. Conclusion: Our findings suggest asymptomatic anorectal CT and/or NG 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.