OBJECTIVES: Mental health is a largely neglected issue among in Sub-Saharan Africa, especially among key populations at risk for HIV. The aim of this study was to estimate the prevalence of psychological distress (PD) and to assess the factors associated among males who have sex with males (MSM), female sex workers (FSW) and drug users (DU) in Togo in 2017. STUDY DESIGN: A cross-sectional bio-behavioral study was conducted in August and September 2017 using a respondent-driven sampling (RDS) method, in eight cities in Togo. METHODS: A standardized questionnaire was used to record sociodemographic characteristics and sexual behaviors. The Alcohol Use Disorders Identification Test (AUDIT) and a subset of questions from the Tobacco Questions for Survey were used to assess alcohol and tobacco consumption respectively. PD was assessed with the Kessler Psychological Distress Scale. A blood sample was taken to test for HIV. Descriptive statistics, univariable and multivariable ordinal regression models were used for analysis. RESULTS: A total of 2044 key populations including 449 DU, 952 FSW and 643 MSM with a median age of 25 years, interquartile range (IQR) [21-32] were recruited. The overall prevalence of mild PD among the three populations was 19.9% (95%CI = [18.3-21.8]) and was 19.2% (95%CI = [17.5-20.9]) for severe/moderate PD. HIV prevalence was 13.7% (95%CI = [12.2-15.2]). High age (≥ 25 years) [aOR = 1.24 (95% CI: 1.02-1.50)], being HIV positive [aOR = 1.80 (95% CI: 1.31-2.48)] and hazardous alcohol consumption [aOR = 1.52 (95% CI: 1.22-1.87)] were risk factors for PD. Secondary [aOR = 0.52 (95% CI: 0.42-0.64)] or higher [aOR = 0.46 (95% CI: 0.32-0.64)] education levels were protective factors associated with PD. FSW [OR = 0.55 (95% CI: 0.43-0.68)] and MSM [OR = 0.33 (95% CI: 0.24-0.44)] were less likely to report PD compared with DU. CONCLUSION AND RECOMMENDATIONS: This is the first study conducted among a large, nationally representative sample of key populations in Togo. The prevalence of PD is high among these populations in Togo and was associated to HIV infection. The present study indicates that mental health care must be integrated within health programs in Togo with a special focus to key populations through interventions such as social support groups.