We empirically analyze the relationship between HIV prevalence and life expectancy in South Africa, using annual data from 1990 to 2025 obtained from the World Data Bank. Employing a Cointegration analysis model, we treat life expectancy at birth (years) as the dependent variable and HIV prevalence (% of population ages 15–49) as the independent variable. Results from the Johansen Cointegration tests confirm the existence of a long-run equilibrium relationship between life expectancy and prevalence of HIV. Specifically, the normalized cointegrating equation shows that a 1% increase in HIV prevalence reduces life expectancy by approximately 4.7 years. Granger causality tests further reveal that HIV prevalence Granger-causes life expectancy, while life expectancy does not Granger-cause HIV prevalence indicating that changes in HIV prevalence predict future changes in life expectancy. We recommend sustained investment in HIV prevention and treatment programs to improve population health outcomes in South Africa.