Research suggests that early family relationships have critical influences on later physical and psychological health, but most studies have focused on the influence of mothers ignoring the unique impacts of fathers. One mechanism by which families may transmit risk is by repeated activation of the hypothalamic-pituitary-adrenal (HPA) axis in the short-term that leads to adult neurobiological dysregulaton, evident in hyper- or hypo-cortisol levels. Using 218 father-child dyads from the Parent and Youth Study (PAYS), the current study investigated whether father involvement in adolescence predicted youth cortisol AUCg and reactivity to a stress task in young adulthood, and whether this relation was mediated by youth perceptions of mattering to their fathers in adolescence. Results revealed that higher father-reported father involvement predicted lower cortisol AUCg in youth when mattering was included in the model, although father involvement was not a statistically significant predictor of AUCg or cortisol reactivity when mattering was not included. Additionally, children who reported higher father involvement also reported higher feelings of mattering, but this association was only statistically significant for girls and European American youth. Youth feelings of mattering did not predict their cortisol reactivity or AUCg in young adulthood. Results suggest that future research should include fathers when investigating the effects of family relationships on youth psychophysiological development.