We sought to identify differences in health-related quality of life (HRQoL) among a sample of HIV positive individuals receiving case management services in northern Florida. Our study consisted of 97 individuals receiving HIV case management that included 56 males (57.7%) and 81 African Americans (83.5%) who were 47.05 years old (SD=9.33). HRQoL was measured using the HIV/AIDS Targeted-Quality of Life scale (HAT-QOL). Results show significant group differences in HRQoL by race, income, tobacco use, alcohol use, drug use, and CD4 cell count, despite only 43% of this sample being able to recall their most recent CD4 count. Translating these findings to inform practice, HIV care providers need to provide continuing education to patients about their disease status, knowledge, and treatment as it relates to self-care. Also, HIV care providers should be especially cognizant of the impact that tobacco, alcohol, and illicit drug use has on HRQoL for persons living with HIV/AIDS (PLHA) by working to assess social support, identify readiness for change, and make appropriate referrals for treatment.