There has been growing concern over sports-related brain injuries and their long-term effects. However, the cumulative effect of sub-concussive hits on the brain is still poorly understood. Twenty-one male Division I collegiate football athletes completed T1 volumetric and arterial spin labeling MRI scans at freshman year with follow-up 2-3 years later. Significant reductions in both brain global and regional cortical volumes were observed. Interestingly, cerebral blood flow was significantly reduced in regions associated with the default-mode network. These changes point to potential long-term effects of sub-concussive hits on the brain.