Positive feelings about work and family responsibilities benefit psychological well-being, but their physical health effects remain unexplored. The study assessed whether meaningful work and reward from taking care of family benefitted physical health to the same degree as mental health. Participants were 181 Danes aged 49-51. Participants reported on working conditions, providing care to family, depressive symptoms, and perceived stress. Physical health was operationalized as a physiological dysregulation (e.g., hypertension, high levels of blood sugar and cholesterol, high body mass index). A multidimensional index of physiological dysregulation was created using parameters of cardiovascular, metabolic, and immune function. As expected, meaningful work and sense of reward from taking care of family members were associated with better mental health. However, in women, the very same factors were positively associated with higher physiological dysregulation. We conclude that work and family factors promoting psychological well-being may have physical health trade-offs, particularly in women.