PurposeInformal family and community support deriving from social relations can play an important role in protecting mental and physical health in resource‐scarce contexts and may help facilitate health service access and uptake. Yet, to date, there has been surprisingly little empirical research investigating the role of social support as a resource for health inHIV‐affectedSouthernAfrican communities, despite the known importance of social connectedness, high rates of physical and mental health conditions, and existing ‘treatment gaps’.MethodsThis paper brings together and discusses findings of multiple linked analyses, from the first large‐scale explanatory sequential mixed methods research investigating the relationship between social support and health with caregiver populations inHIV‐endemicSouthAfrica.ResultsOverall, findings highlight the protective role of social support for caregiver mental health, the multiple perceived psychological and behavioural mechanisms possibly explaining the relationship between social support and both mental and physical health, and gender differences in the provision, effects, and availability of support.ConclusionsDrawing from these findings and the broader literature, four potential foci for future research inSouthernAfrica are identified and discussed, as are implications for research design and methodologies. These involve achieving a better understanding of the following: The pathways and processes explaining common and differential effects of social support across different population groups; the potential protective role of social support for physical health; and the role of factors such as gender and social and cultural norms in shaping the relationship between social support and health.Statement of contributionWhat is already known on this subject?Mental and physical health are closely related.HIVincreases the risk of mental health conditions.Studies mainly from high‐income countries have shown social relations and support to be protective of health.What does this study add?First mixed methods research of this dimension on social support and health inSouthernAfrica.Highlights importance of social support for mental health among caregivers of children inHIV‐endemicSouthAfrica.Points to biological and psychological pathways explaining the support–health relationsh