Youth with multiple sclerosis (MS) often experience cognitive impairment and psychosocial disturbances. We describe the relationship between memory function, psychosocial skills, and brain volume in 32 patients with pediatric-onset MS and 30 controls. Amygdala volume was significantly lower in patients compared with controls. In general, poorer memory was associated with reduced functional communication skills and reduced amygdala volume. Greater amygdala volume in patients correlated with parent-reported functional communication and social skills. Adjusting for whole-brain volume, right amygdala volume was positively associated with visual memory; left amygdala volume was a stronger predictor of parent-reported social skills.