OBJECTIVE: To examine a cohort of HIV+ study participants, who are caregivers (CGs) and non-caregivers (NCGs), to determine whether differences exist across their sociodemographic backgrounds, immune functioning, and quality-of-life (i.e., symptom distress, physical, and mental quality-of-life). METHODS: A secondary analysis of the cross-sectional subset of the population-based Collaborations HIV Outcomes Research US Cohort (CHORUS). Sample consists of 5521 HIV+ adults; median age 43 years (SD 8.7); 88.6% male; 70.7% non-Hispanic White, 17.6% African-American, and 7.8% Hispanic. Measures include the HIV Symptom Distress Scale and the SF-12. Analytical models included t-tests and multivariate linear regression. RESULTS: HIV+ CGs have lower educational attainment than HIV+ NCGs (p=0.02). Seropositive CGs also experience greater HIV symptom distress (adjusted p<0.006) and poorer physical quality-of-life (adjusted p<0.001) than their seropostive NCG counterparts. CONCLUSION: HIV+ CGs may require different supportive services than HIV+ NCGs, suggesting a need to develop tailored interventions to address modifiable factors, such as lower education and poor physical health. Both of these factors have been associated with suboptimal antiretroviral adherence, suggesting a role for the routine screening of adherence predictors amongst HIV+ CGs. These findings may have more relevance in resource-poor settings where the prevalence of HIV is higher, with a likely growing population of informal and family CGs infected with HIV.