This study examined the mediating role of loneliness (assessed by self-report at Time 2; Grade 6) in the relation between early social preference (assessed by peer report at Time 1; kindergarten through Grade 3) and adolescent anxious/depressed symptoms (assessed by mother, teacher, and self-reports at Time 3; Grades 7–9). Five hundred eighty-five boys and girls (48% female; 16% African American) from three geographic sites of the Child Development Project were followed from kindergarten through Grade 9. Loneliness partially mediated and uniquely incremented the significant effect of low social preference in childhood on anxious/depressed symptoms in adolescence, controlling for early anxious/depressed symptoms at Time 1. Findings are critical to understanding the psychological functioning through which early social experiences affect youths' maladjusted development. Directions for basic and intervention research are discussed, and implications for treatment are addressed.