The present study assessed the moderating role of depressive symptomology in the interactive role of John Henryism (i.e., persistent striving with daily psychosocial demands) and father's educational attainment in estimated cardiorespiratory fitness in women. Two hundred one female Midwestern college students completed online psychosocial surveys. Among high-John Henryism women who were depressed, higher father's education levels predicted better fitness. Conversely, higher father's education predicted worse fitness for nondepressed low-John Henryism women. Depression may moderate the role of John Henryism and socioeconomic status in health, with higher John Henryism and education associated with optimal health for depressives.