Combination HIV prevention and treatment interventions (CHIs) have led to substantial declines in HIV incidence in sub-Saharan Africa; however, population-level data on non-HIV sexually transmitted infections (STIs) in the context of CHIs are rare. We aimed to assess STI burden following scale-up of CHIs in Uganda. The Sexually Transmitted Infection Prevalence Study (STIPS) was a cross-sectional study nested within a population-based cohort among inland agrarian and Lake Victoria fishing populations in southern Uganda. STIPS enrolled consenting residents aged 18-49 years in two communities (one inland and one fishing) between May and October, 2019, and measured the prevalence of chlamydia, gonorrhoea, trichomonas, syphilis, and herpes simplex virus 2 (HSV-2). Between May 27, 2019 and Oct 25, 2019, STIPS enrolled 1825 participants. HIV prevalence was 14·0% among the inland population and 39·8% among the fishing population, with about 90% HIV viral load suppression in both communities. Among inland and fishing populations, chlamydia prevalence was 9·6% (95% CI 7·9-11·7) and 9·9% (8·1-12·0), gonorrhoea prevalence 5·0% (3·8-6·7) and 8·4% (6·8-10·5), trichomonas prevalence 9·4% (7·7-11·5) and 12·2% (10·2-14·5), and HSV-2 prevalence 43·0% (39·9-46·3) and 64·4% (61·3-67·6), respectively. In the fishing population, syphilis seropositivity was 24·2% (21·5-27·2) with 9·4% (7·7-11·5) having high-titre (rapid plasma reagin ≥1:8) infection, including 16·9% (11·9-24·0%) of men living with HIV. Prevalence of at least one curable STI (chlamydia, gonorrhoea, trichomonas, or high-titre syphilis) was 51% higher among people living with HIV (vs HIV negative; adjusted prevalence risk ratio [PRR] 1·51; 95% CI 1·27-1·78), including among pregnant women (adjusted PRR 1·87, 1·11-3·17), with no differences by HIV suppression status. Despite near universal HIV treatment, STI burden remains extremely high in southern Uganda, particularly among people living with HIV. There is an urgent need to integrate STI care with HIV services in African settings. National Institutes of Health.