IntroductionPeer support can help navigate the isolation and psychological strain frequently experienced by youth living with chronic illness. Yet, data are lacking on the impact of providing support for youth living with mixed chronic conditions. We assessed the acceptability, feasibility and preliminary mental health impacts of a clinic‐based peer support group for South African youth living with chronic illnesses, including HIV.MethodsThis mixed‐methods pilot study (September 2021–June 2022) enrolled 58 young patients, ages 13–24, at an urban hospital in Cape Town, South Africa. In‐depth interviews elicited the perspectives of 20 young people in relation to their participation in the Better Together programme, a recurring clinic‐based peer support group for patients with mixed chronic illnesses. Self‐reported resilience, attitudes towards illness, stigma and mental health were captured via established measures. T‐tests and multivariate analysis of variance compared psychosocial outcomes for 20 group participants and 38 control patients, controlling for socio‐demographic characteristics at enrolment. Logistic regression analyses estimated the predicted probability of a positive depression or anxiety screening given peer group participation.ResultsAll interviewees valued being able to compare treatment regimens and disease management habits with peers living with different conditions. Adolescents living with HIV stated that understanding the hardships faced by those with other conditions helped them accept their own illness and lessened feelings of isolation. Compared to patients who did not participate in Better Together, those who attended ≥5 groups had statistically significantly higher individual‐level resilience, a more positive attitude towards their illness(es), lower internalised stigma and a more positive self‐concept. The probability of being screened positive for depression was 23.4 percentage points lower (95% CI: 1.5, 45.3) for Better Together participants compared to controls; the probability of a positive anxiety screening was 45.8 percentage points lower (95% CI: 18.1, 73.6).ConclusionsRecurring, clinic‐based peer support groups that integrate youth living with HIV and other chronic diseases are novel. Group sustainability will depend on the commitment of experienced peer leaders and providers, routine scheduling and transportation support. A fully powered randomised trial is needed to test the optimal implementation and causal mental health effects of the Better Together model.