Out-of-pocket health (OOP) expenditure in Nigeria poses a significant financial burden on households, especially those with members living with HIV/AIDS. To assess the macroeconomic factors associated with OOP health spending, the ADRL approach was adopted using the Grossman’s Model as the baseline equation, and the scope of the study was 1986-2025. Independent variables included HIV/AIDS prevalence rate, literacy rate, life expectancy, and public health expenditure, with OOP as the dependent variable. Data were sourced from the Central Bank of Nigeria's Statistical Bulletin, Annual Reports, and National Bureau of Statistics, along with World Development Indicators and International Financial Statistics. The Autoregressive Distributed Lag (ARDL) method revealed that higher HIV/AIDS prevalence is associated with OOP expenses, while literacy rate and life expectancy have no association. Also, increased public health spending reduces OOP spending on health. Based on these findings, the study recommends increased public spending on health, and strengthen supports for HIV/AIDS programme as a strategy to reduce the burden of OOP health spending.