TBI results in significant cognitive impairments and in altered brain functional connectivity. However, no studies explored so far, the relationship between global functional connectivity and cognitive outcome in chronic moderate-severe TBI. This proof of principle study employed the intrinsic connectivity contrast, an objective voxel-based metric of global functional connectivity, in a small sample of chronic moderate-severe TBI participants and a group of healthy controls matched on gender (males), age, and education. Cognitive tests assessing executive functions, verbal memory, visual memory, attention/organization, and cognitive reserve were administered. Group differences in terms of global functional connectivity maps were assessed and the association between performance on the cognitive measures and global functional connectivity was examined. Next, we investigated the spatial extent of functional connectivity in the brain regions found to be associated with cognitive performance, using traditional seed-based analyses. Global functional connectivity of the TBI group was altered, compared to the controls. Moreover, the strength of global functional connectivity in affected brain areas was associated with cognitive outcome. These findings indicate that impaired global functional connectivity is a significant consequence of TBI suggesting that cognitive impairments following TBI may be partly attributed to altered functional connectivity between brain areas involved in the specific cognitive functions.