BackgroundPoor psychological well-being, including depression, anxiety, and low self-esteem, is both prevalent among young South Africans living with HIV and associated with poor HIV clinical outcomes. By impacting food insecurity and employment, the COVID-19 pandemic may have influenced psychological well-being in this population. This analysis sought to examine whether food insecurity and unemployment mediated the relationship between study cohort (pre- versus during-pandemic) and psychological well-being in our sample of young South Africans living with HIV.MethodsThis was a secondary analysis comparing baseline data from two cohorts of young South Africans ages 18–24 from the Cape Town and East London metro areas who tested positive for HIV at clinics (or mobile clinics) either before or during the COVID-19 pandemic. Baseline sociodemographic, economic, and psychological outcomes were analyzed through a series of bivariate logistic regression and mediation analyses. All data were analyzed in 2023 and 2024.ResultsReported food anxiety, insufficient food quality, and insufficient food quantity were lower in the cohort recruited during the COVID-19 pandemic than those recruited before the pandemic (p < 0.001). Higher levels of food insecurity predicted higher depressive and anxiety symptoms and lower self-esteem. Food anxiety, insufficient food quality, and insufficient food quantity, but not unemployment, mediated the relationship between study cohort and depressive symptoms, anxiety symptoms, and self-esteem.ConclusionFood insecurity may have decreased amongst our sample of young people during the COVID-19 pandemic. Our findings build on our understanding of how the psychological well-being of young people living with HIV was affected by the COVID-19 pandemic and may lend support to interventions targeting food insecurity to improve psychological well-being in this population.