Depression is one of the most frequently reported and distressing residual complaints in survivors of head injury. Studies investigating the pattern of neuropathology associated with depression post head injury have found little consistency. One explanation for this is that cognitive reserve "protects" against depression either through more efficient processing or more effective compensation. An alternative explanation is that previous studies have used relatively gross measures of lesion location, and variable inclusion criteria and times between scan and injury. This study explored these possibilities in a cohort of survivors of moderate-severe head injury at least 6 months post-injury. Volunteers completed neuropsychological assessments and structural magnetic resonance imaging (MRI) scans. A significant difference between depressed and non-depressed survivors was found, with higher intelligence associated with lower rates of depression. No significant anatomical differences were found between depressed and non-depressed survivors. These results suggest that premorbid intelligence may provide a resilience factor against depression in head injury survivors.