Epidemiological data suggest that the prevalence of autoimmune diseases is increasing. Although evidence implies that people with chronic illnesses experience higher levels of burnout, there are few available insights for developing preventative interventions. This paper builds on the Conservation of Resources (COR) and the Job Demands-Resources (JD-R) framework to investigate the association between impaired health, burnout, and work engagement. In two studies, we research the role of health status as a resource, respectively, autoimmune illness symptom severity as a diminished resource, and investigate its variance explanation in burnout and work engagement above and beyond the effects of job demands and resources. Study 1 investigated the hypotheses among 87 employees with inflammatory bowel diseases. Controlling for job demands and resources, symptom severity was positively associated with (exhaustion) burnout and negatively associated with work engagement. In Study 2, we applied mixed model analyses using a sample of 129 employees with multiple sclerosis. We found significant associations of symptom severity on burnout and vigor work engagement above and beyond the effects of job demands and social support. Our studies provide important insights for employees with chronic illnesses and the organizations in which they work and give indications for theory development, future research, and the development of interventions.