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STUDY OBJECTIVES Insufficient sleep and social stress are associated with weight gain and obesity development in adolescent girls. Functional magnetic resonance imaging (fMRI) research suggests that altered engagement of emotion-related neural networks may explain overeating when under stress. The purpose of this study is to explore the effects of acute sleep restriction on female adolescents' neural responding during social evaluative stress and their subsequent eating behavior. METHODS Forty-two adolescent females (ages 15-18 years) with overweight or obesity completed a social stress induction task in which they were told they would be rated by peers based on their photograph and profile. Participants were randomly assigned to one night of sleep deprivation or 9 hours of sleep the night before undergoing fMRI while receiving positive and negative evaluations from their peers. After which, subjects participated in an ad libitum buffet. RESULTS Sleep deprived, relative to non-deprived girls had distinct patterns of neural engagement to positive and negative evaluation in anterior, mid, and posterior aspects of midline brain structures. Moreover, a sleep deprivation-by-evaluation valence-by-caloric intake interaction emerged in bilateral dorsal anterior cingulate. Among sleep deprived girls, greater engagement during negative, but not positive, feedback was associated with lower caloric intake. This was not observed for non-sleep deprived girls. CONCLUSIONS Results suggest an interaction between acute sleep loss and social evaluation that predicts emotion-related neural activation and caloric intake in adolescents. This research helps to elucidate the relationship between sleep loss, social stress, and weight status using a novel health neuroscience model.