Fifteen million children have been orphaned by AIDS. A growing body of evidence documents impacts of parental deaths on orphans, but little is known about impacts faced by AIDS-orphan carers. This study set out to: (a) investigate physical and mental health outcomes of adults caring for children in Umlazi, a high HIV prevalence township in South Africa; (b) assess whether AIDS-orphan carers face worse outcomes compared to other carers; and, (c) identify risk and protective factors for health. Using a cross-sectional survey, data was gathered from a representative community sample from August 2008 to March 2009 resulting in the largest known study conducted on AIDS-orphan carers to date (n=1599). The majority of carers looked after non-orphaned children (66.85%) followed by AIDS-orphan (22.45%) and other-orphan children (10.69%). Orphan carers had significantly worse general health and functioning, depression, and post-traumatic stress than non-orphan carers but patterns were less clear when orphan carers were disaggregated into AIDS-orphan and other-orphan carers for comparison. This suggests that health interventions might target orphan carers, rather than singling out AIDS-orphan carers. Differences in age, gender, education, economic assets, and source of household income fully accounted for the association between being an orphan carer and poor health. Social policy grants reduced negative health disparities between orphan carers and non-orphan carers. Social support, education, economic assets, food, access to water, and housing were iii also identified as risk and protective co-factors that might reduce orphan carer disparities in health. By highlighting health as a serious issue for orphan carers and identifying risk and protective factors for health, this study offers policy and program insights into how to mitigate negative impacts faced by carers in high HIV prevalence communities facing escalating numbers of orphans.