This study extends social-psychological research on social networks and mental health by examining cross-gender differences in social integration and depression among United Methodist clergy in North Carolina. Using data from the fifth wave of the Clergy Health Initiative panel survey, we used cross-group models to examine the association of depressive symptoms and network in-degree, out-degree, and perceived social isolation among men (N = 1,145) and women (N = 535) clergy. The analysis reveals gendered differences in this association. Specifically, out-degree bore a significant negative relationship with depressive symptoms for men but not women. Feeling socially isolated had a significant positive association with depression in both men and women.