The job demands-resources (JD-R) model has rarely been used in conjunction with physiological indicators of stress and ill-health. This study explored the associations between the JD-R model and physiological indicators of the stress response, while considering potential moderators of this relationship. Across 2 timepoints (summer-winter) direct-care workers completed questionnaires assessing job demands, job resources, empathy and self-efficacy, and provided morning saliva samples to assess physiological indices of stress and ill-health. Changes in job resources and empathy were positively correlated with changes in the cortisol awakening response (CAR). Further, changes in both job resources and empathy independently buffered the impact of higher job demands on increased salivary alpha amylase awakening response (sAA-AR) concentrations. These findings suggest that despite increased job demands, the sAA-AR decreased for direct-care workers that had perceived high job resources or who reported higher empathy. Potentially, job resources and empathy may act as a protective factor against the development of poor health associated with workplace stress.