Objective: Weight change is common during the first year of college and may be related to different outcomes for men and women. This study examined the moderating effects of gender on the association between weight change and college adjustment and depressive symptoms. Participants: One-hundred and eighty-one 18-19-year-old college freshmen (56.9% female; 84.5% Caucasian). Methods: Students completed a one-time survey about demographics, weight, college adjustment, and depressive symptoms during their second semester of college. Results: Increased weight change was associated with fewer depressive symptoms for both men and women (p < 0.04). For men, increased weight change was associated with better overall college adjustment, more positivity about college, less negativity about college, and less homesickness (all p < 0.02). Conclusions: Universities could target men and women differently in regard to weight, college adjustment, and mental health to promote a positive college experience and optimal mental health.