This study examined the effect of health-related stress on changes in religiousness in a sample of elderly, medically ill patients. Patients admitted to Duke University Medical Center (N = 745) were interviewed at baseline and 3-month follow-up. Increases in illness severity (from baseline to follow-up) were associated with decreases in both organizational and private religiousness at follow-up. Effect of illness severity on organizational religiousness was statistically mediated by changes in physical activity, while its effect on private religiousness remained significant after controlling for physical activity. These findings encourage further research investigating causal relationships between stress and religion, as well as identifying measures of religiousness that may capture this construct in the medically ill population.