BACKGROUND: Women live on average five years longer than men, and the sex difference in longevity is typically lower in populations with high mortality. South Africa-a high mortality population with a large sex disparity-is an exception, but the causes of death that contribute to this difference are not well understood. METHODS: Using data from a demographic surveillance system in rural KwaZulu-Natal (2000-2014), we estimate differences between male and female adult life expectancy by HIV status. The contribution of causes of death to these life expectancy differences are computed with demographic decomposition techniques. Cause of death information comes from verbal autopsy interviews that are interpreted with the InSilicoVA tool. RESULTS: Adult women lived an average of 10.4 years (95% confidence Interval 9.0-11.6) longer than men. Sex differences in adult life expectancy were even larger when disaggregated by HIV status: 13.1 (95% confidence interval 10.7-15.3) and 11.2 (95% confidence interval 7.5-14.8) years among known HIV negatives and positives, respectively. Elevated male mortality from pulmonary tuberculosis (TB) and external injuries were responsible for 43% and 31% of the sex difference in life expectancy among the HIV negative population, and 81% and 16% of the difference among people living with HIV. CONCLUSIONS: The sex differences in adult life expectancy in rural KwaZulu-Natal are exceptionally large, atypical for an African population, and largely driven by high male mortality from pulmonary TB and injuries. This is the case for both HIV positive and HIV negative men and women, signalling a need to improve the engagement of men with health services, irrespective of their HIV status.