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Globally, mental health problems have been reported to be more common in youth living with HIV (YLWH) than in the general population, but routine mental health screening is rarely done in high-volume HIV clinics. In 2019, YLWH in a large HIV clinic in Botswana were screened using the Generalized Anxiety Scale-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) in a pilot standard-of-care screening programme. Two-way ANOVA was used to describe the effects of age group (12-<16, 16-<20 and 20-25 years old) and sex on GAD-7 and PHQ-9 scores. Chi-square statistics were used to compare characteristics of YLWH with and without potential suicidality/self-harm symptoms based on question 9 in the PHQ-9. Among 1 469 YLWH, 33.1%, 44.3% and 15.0% had anxiety, depression and potential suicidality/self-harm symptoms respectively. YLWH of 20-25 years old and 16-<20 years old had higher GAD-7 scores compared to 12-<16-year-olds ( = 0.014 and = <0.001 respectively). Female YLWH of 20-25 years old had higher PHQ-9 scores compared to 12-<16-year-olds ( = 0.002). There were no other sex-age dynamics that were statistically significant. Female YLWH endorsed more thoughts of suicidality/self-harm than males (17% versus 13%, = 0.03 respectively). Given the proportion of YLWH with mental health symptoms, Botswana should enhance investments in mental health services for YLWH, especially for young female adults who bear a disproportionate burden.