Too many people with HIV have left the job market permanently and those with reduced work capacity have been unable to keep their jobs. There is a need to examine the health effects of labor force participation in people with HIV. This study presents longitudinal data from 1,415 HIV-positive men who have sex with men taking part in the Multicenter AIDS Cohort Study. Generalized Estimating Equations show that employment is associated with better physical and mental health quality of life and suggests that there may be an adaptation process to the experience of unemployment. Post hoc analyses also suggest that people who are more physically vulnerable may undergo steeper health declines due to job loss than those who are generally healthier. However, this may also be the result of a selection effect whereby poor physical health contributes to unemployment. Policies that promote labor force participation may not only increase employment rates but also improve the health of people living with HIV.