The objective of this study is to investigate the relationships between burnout, ill health, job demands and resources, and dispositional optimism in a higher education institution in South Africa. A survey design was used. The study population (N = 279) consisted of academic staff working in a higher education institution. The Maslach Burnout Inventory-General Survey, The Life Orientation Test-Job Demands-Resources Scale and the Health subscale of the ASSET were used as measuring instruments. A good fit was found for a model in which burnout (exhaustion and cynicism) mediated the relationship between perceived high job demands and low availability of job resources, and ill health. Dispositional optimism had direct effects on burnout and ill health. (Contains 4 tables, 1 figure, and 1 note.)