Alterations of social cognition and dysfunctional interpersonal expectations are thought to play an important role in the etiology of depression and have, thus, become a key target of psychotherapeutic interventions. The underlying neurobiology, however, remains elusive. Based upon the idea of a close link between affective and introspective processes relevant for social interactions and alterations thereof in states of depression, we used a meta-analytically informed network analysis to investigate resting-state functional connectivity in an introspective socio-affective (ISA) network in individuals with and without depression. Results of our analysis demonstrate significant differences between the groups with depressed individuals showing hyperconnectivity of the ISA network. These findings demonstrate that neurofunctional alterations exist in individuals with depression in a neural network relevant for introspection and socio-affective processing, which may contribute to the interpersonal difficulties that are linked to depressive symptomatology.