In modern society, work stress is highly prevalent. Problematically, work stress can cause disease. To help understand the causal relationship between work stress and disease, we present a computational model of this relationship. That is, drawing from allostatic load theory, we captured the link between work stress and disease in a set of mathematical formulas. With simulation studies, we then examined our model's ability to reproduce key findings from previous empirical research. Specifically, results from Study 1 suggested that our model could accurately reproduce established findings on daily fluctuations in cortisol levels (both on the group level and the individual level). Results from Study 2 suggested that our model could accurately reproduce established findings on the relationship between work stress and cardiovascular disease. Finally, results from Study 3 yielded new predictions about the relationship between workweek configurations (i.e., how working hours are distributed over days) and the subsequent development of disease. Together, our studies suggest a new, computational approach to studying the causal link between work stress and disease. We suggest that this approach is fruitful, as it aids the development of falsifiable theory, and as it opens up new ways of generating predictions about why and when work stress is (un)healthy.