Background: Kenya, like many countries, shuttered schools during COVID–19, with subsequent increases in poor mental health, sexual activity, and pregnancy. We sought to understand how the COVID–19 pandemic may mediate risk of reproductive tract infections. We hypothesized that greater COVID–19 related stress would mediate risk via mental health, feeling safe inside the home, and sexual exposure, given the pandemic mitigation–related impacts of school closures on these factors. Methods: We analyzed data from a cohort of 436 girls enrolled in secondary school in rural western Kenya. Baseline, 6–, 12–, and 18– month study visits occurred April 2018 – December 2019 (pre–COVID), and 30–, 36–, and 48– month study visits occurred September 2020 – July 2022 (COVID period). At study visits, participants self–completed a survey for sociodemographics and sexual practices, and provided self–collected vaginal swabs for Bacterial vaginosis (BV) testing, with STI testing at annual visits. COVID–related stress was measured with a standardized scale and dichotomized at highest quartile. Mixed effects modeling quantified how BV and STI changed over time, and longitudinal mediation analysis quantified how the relationship between COVID–19 stress and increased BV was mediated. Findings: BV and STI prevalence increased from 12.1% and 10.7% pre–COVID to 24.5% and 18.1% during COVID, respectively. This equated to a 26% (95% CI 1.00 – 1.59) and 36% (95% CI 0.98 – 1.88) increased relative prevalence of BV and STIs, respectively, in the COVID–19 period compared to pre–COVID, adjusted for numerous sociodemographic and behavioral factors. Higher COVID–related stress was associated with elevated depressive symptoms and feeling less safe inside the home, which were each associated with increased likelihood of having a boyfriend. In longitudinal mediation analyses, the direct effect of COVID–related stress on BV was small and non–significant, indicating increased BV was due to the constellation of factors that were impacted during the COVID pandemic. Conclusions: In this cohort of adolescent girls, BV and STIs increased following COVID–related school closures. These results highlight modifiable factors to help maintain sexual and reproductive health resiliency, such as anticipating and mitigating mental health impacts, domestic safety concerns, and maintaining sexual health services to prevent and treat reproductive tract infections.