Although previous data indicate that dyadic coping is associated with Hypothalamic-Pituitary-Adrenal (HPA-axis and C-reactive protein (CRP) separately, no study has reported on the ratio between these two systems and dyadic coping, despite this index of physiological homeostasis being associated with physical health and depression. Forty-eight community volunteers who were either married (n = 36) or cohabiting (n = 12) provided saliva and serum samples, and also completed a dyadic coping inventory. There was a significant inverse correlation between cortisol:CRP ratio and dyadic coping, but only for married participants. One of the six dyadic coping items, related to being able to calmly discuss something within a dyad, was the key factor in the association between dyadic coping and cortisol:CRP ratio. These findings provide some initial support for the influence of the way that spouses interact to solve problems and the balance between their HPA and immune systems.