PurposeThe current study examined the relationships between health-related quality of life (HRQOL) and social determinants of health (SDH), which are the individual and structural factors that contribute to health outcomes.MethodA hierarchical general linear model was used to assess the sequential effect of the SDH on the scores of the Short Form-12 among people living with HIV.ResultsResults show that many psychosocial, medical, demographic, financial, and vocational factors are significant predictors of HRQOL.ConclusionsGaining a deeper understanding of the impact of SDH on HRQOL is critical for rehabilitation counselors to develop effective assessments and interventions.