This study examined the role of low social preference in relation to subsequent depressive symptoms, with particular attention to prior depressive symptoms, prior and concurrent aggression, mutual friendships, and peer victimization. Italian children (N = 288) were followed from grade 6 through grade 8, and American children (N = 585) were followed from kindergarten through grade 12. Analyses demonstrate that low social preference contributes to later depressive symptoms. The effects are not accounted for by depressive symptoms or aggression experienced prior to low social preference but are mostly accounted for by the co-occurrence of depressive symptoms with concurrent aggressive behavior; gender, mutual friendships, and peer victimization generally did not moderate these associations. We conclude that peer relationship problems do predict later depressive symptoms, and a possible mechanism through which this effect occurs is through the effect of poor peer relationships on increasing aggressive behavior, which is associated with depressive symptoms.