Bipolar disorder (BD) is a complex psychiatric illness; in addition to mood disturbances, people with this illness experience cognitive dysfunction and neurovegetative shifts. Some people with BD experience difficulty in interpersonal relationships. Impairment in social cognition may contribute to these difficulties in interpersonal functioning. In order to examine the neural and behavioral correlates of social cognition in patients with BD, a social cognition task was administered to 25 healthy controls (HCs) and 25 patients with BD and depression scores ranging from euthymic to depressed at the time of assessment. The task required participants to evaluate situations that were “enhancing” or “threatening” to self-esteem. Patients differed significantly from HCs in their evaluation of threatening scenarios, directed at both oneself and at other people (p<0.001). Neuroimaging results reveal differential patterns of prefrontal-cortical and limbic-subcortical activation in patients [p<0.001]. Findings may contribute to understanding alterations in social cognitive functioning in patients with BD.