An association between stress and health has been hypothesized. However, the association pathways are unclear. In this article, the authors examined the associations between stress, social support, and cortisol and the mediating effect of several psychosocial variables. Adult men and women (n = 146) completed psychosocial surveys and provided saliva samples for cortisol assessments, quarterly, for 1 year Cross-sectional analysis results showed an inverse relationship between basal cortisol and stress (Model 1: coefficient = -.068, SE = .024, p = .006). After controlling for stress, the authors also found an inverse relationship between basal cortisol and social support among individuals with high social support (upper tertile compared with 1st and 2nd tertiles) (Model 2: coefficient = -.440, SE = .155, p = .005). Longitudinal models showed similar findings for both associations. These findings do not support the general hypothesis of a negative effect of chronic intermittent stress on health through Hypothalamic Pituitary Adrenal (HPA) axis activation, but do support a positive effect of social support on the HPA axis. Both findings deserve further investigation.