CONTEXT: Congenital adrenal hyperplasia (CAH) is a genetic disorder that results in hormonal imbalances and decreased brain volumes in regions important for emotional processing. OBJECTIVE: To examine whether emotion perception differs between youth with CAH and control youth, and if these differences relate to brain volumes. METHODS: In this cross-sectional study of 27 youths with CAH (mean age = 12.63 years, 16 female) and 35 age- and sex-matched controls (mean age = 13.03 years, 20 female), each participant rated picture stimuli and completed a 3T structural brain scan. Valence and arousal ratings and reaction times of 61 affective images were assessed. Gray matter volumes were measured by MRI. RESULTS: Youth with CAH had lower valence ratings for negative (P =.007) and neutral (P =.019) images. Controls showed differences in reaction times and arousal ratings across stimuli conditions, but youth with CAH did not. Brain volumes of the right amygdala (P =.025) and left hippocampus (P =.002) were associated with valence ratings. Left rostral middle frontal (P <.001) and right medial orbitofrontal cortex (P =.002) volumes were negatively related to valence scores only in youth with CAH, whereas left medial orbitofrontal cortex (P <.001) volumes were associated with valence scores positively in youth with CAH and negatively in controls. CONCLUSION: Findings suggest that youth with CAH perceive emotive stimuli as more unpleasant. Decreased brain volumes in the amygdala, hippocampus, and prefrontal cortex are associated with these measures of altered emotion perception in youth with CAH.