INTRODUCTION: Despite the mounting evidence that depression is one of the most common psychiatric sequelae in survivors of traumatic brain injury (TBI), no studies so far have attempted to provide an explanation in terms of functional network integrity. This proof of concept study investigated the association between the severity of depressive symptoms and resting network integrity in a sample of patients with TBI and a group of healthy controls. METHODS: We first examined the association between depression symptomatology and global functional connectivity and then attempted to characterize the extent of differences in functional network integrity. RESULTS: The severity of depressive symptoms in patients with TBI was associated with neuroadaptations within the insula, the thalamus and the subgenual anterior cingulate cortex (ACC). Specifically, patients with TBI displayed increased connectivity between the insula and a region encompassing the rolandic operculum and the superior temporal cortex and reduced connectivity between the thalamus and the dorsolateral prefrontal cortex. CONCLUSIONS: These findings show the network level involvement of the insula, the thalamus and the subgenual ACC in the depressive symptomatology of patients with TBI and tentatively propose that TBI-induced depression may result from altered functional connectivity of a set of networks associated with emotional regulation. However, other factors including a number of adjustment issues and challenges may also lead to depression in this population.