Introduction – In Mayotte, the rate of newly diagnosed HIV infections was 184 per 1,000,000 inhabitants in 2018, and 2.1% of pregnant women tested positive for syphilis in 2007–2008. The objective of this survey is to estimate, for the first time, the prevalence of HIV infection and sexually transmitted infections (STIs) in Mayotte. Method – The survey was conducted from November 21, 2018, to June 14, 2019, among a representative sample of individuals aged 15–69 years using a three-stage sampling design (dwellings, households, individuals). Demographic, socioeconomic, and behavioral data were collected during face-to-face interviews. Blood samples (HIV and syphilis serology) and self-collected vaginal swabs for women or urine samples for men (PCR: Trichomonas vaginalis (Tv), Chlamydia trachomatis (Ct), and Neisseria gonorrhoeae (Ng)) were offered. Weighted univariate and multivariate analyses were performed. Results – Among the 4,643 people who completed the questionnaire, 3,042 (65.5%) were tested for an STI. The prevalence of Ct infections was 9.2% (95% confidence interval, 95% CI: [7.9–10.4]). Risk factors include female gender (adjusted odds ratio – aOR = 1.35 [1.04–1.74]), age between 20 and 29 years (2.99 [1.85–4.84]) or 30 and 49 years (1.91 [1.20–3.04]), lack of a diploma (1.65 [1.02–2.66]), and an educational level below the high school diploma (1.81 [1.06–3.08]). T. vaginalis infection is common (8.1% [7.01–9.2]). It is associated with being female (5.7 [3.7–8.8]), unemployment (2.2 [1.5–3.2]), and economic inactivity (2.2 [1.5–3.2]). Gonorrhea (0.8% [0.3–1.2]) and syphilis (0.4% [0.2–0.6]) are less common. No estimates were made for HIV (3 seropositive cases). Conclusion – These very high prevalence rates highlight the particularly significant burden of Ct and Tv infections in Mayotte. Condom use and regular screening remain essential for the prevention of STIs.