Objectives: The present study on people living with HIV/AIDS (PLWHA) identifies socio-demographic and health-related factors corresponding with their labour market participation. Methods: The study sample bases on a German observational sub-study of 527 male PLWHA. The present analysis is restricted to male PLWHA in working age. By means of a multivariate regression, we identify factors that contribute to unemployment and job loss. Results: The probability to be unemployed is significantly negatively correlated with age above 40 years and graduation from university and positively correlated with problems with daily activities (frailty) and disease severity (CDC stage C). The probability of employment loss during the 2-year observation period is significantly negatively correlated with the educational level, whereas frailty and hepatitis C (HCV) co-infection increase the odds of employment loss. Conclusions: As problems to manage daily activities and disease progression are associated with unemployment, an effective HIV treatment is an important cornerstone for employment. This is also true for the management of comorbidities, such as HCV co-infection, which also negatively affects employment status in our study.