BackgroundPsychological distress is a mental health condition that is common in adolescents. It negatively affects the academic performance of adolescents, relationships with family and friends, and the ability of adolescents to participate fully in the community. Stressful life events in low income countries and risk taking behavior of adolescents have raised concerns on the magnitude and impact of psychological distress among adolescents in Uganda. This study aims to estimate the prevalence of psychological distress and assess the high risk behaviors associated with psychological distress among secondary school students in Uganda. MethodsA community based cross-sectional study was conducted among secondary school students in Mbarara Municipality, Uganda. Multistage cluster sampling technique was used to recruit study participants and a total of 921 students participated in the study using a self-reported questionnaire. Psychological distress was assessed by Kessler’s psychological distress scale (K10). To identify high risk behaviors associated with psychological distress, multinomial logistic regression was used with p <0.05 and 95% confidence interval. ResultsThe prevalence of psychological distress was 57%. Risky sexual behavior, alcohol consumption, smoking and substance use were associated with psychological distress. Also, boarding school students, those in mixed schools, students that own mobile phones and adolescents with chronic illness were more likely to report psychological distress. ConclusionThe prevalence of psychological distress is high among school going adolescents and risky behaviors were associated with psychological distress. The findings suggest the need to address mental health issues in adolescents.