OBJECTIVES: To determine the proportion of under-5 deaths that occurred at home in rural South Africa, whether care was sought prior to death, and determinants of home deaths amongst those who sought care. METHODS: Verbal autopsy data were used for all under-5 deaths, 2000-2015, in two health and demographic surveillance system sites. Trends in place of death and care-seeking were assessed. Associations between sociodemographic factors and home death despite seeking care were assessed by multivariate logistic regressions. RESULTS: There were 3760 under-5 deaths; 1954 (53%) at home and 1510 (41%) in health facilities. Eighty-four per cent of children who died at home accessed healthcare during their final illness. Amongst neonates for whom care was sought, those who were 8-27 days old were more likely to die at home than those who were 0-7 days old (OR = 5.56, 95%CI 2.69-11.55, P < 0.001). Factors associated with home death of infants and young children despite seeking care included low maternal education (OR = 1.71, 95%CI 1.31-2.24, P < 0.001), larger household size (OR = 1.56, 95%CI 1.17-2.06, P = 0.002), traditional medicine use (OR = 2.33, 95%CI 1.75-3.12, P < 0.001) and Mozambican descent (OR = 1.47, 95%CI 1.06-2.03, P = 0.020). The proportion of HIV-related deaths that occurred at home fell from 60% in 2008-2011 to 39% in 2012-2015 ( chi(2) = 13.86, P < 0.001). CONCLUSION: More than half of under-5 deaths in rural South Africa occurred at home although healthcare was sought for most children, highlighting that home deaths are not simply a function of poor care-seeking. Interventions should target high-risk sociodemographic groups.