Carbon monoxide (CO) intoxication can result in cognitive deficits and demyelinating changes of the white matter (WM), for which hyperbaric-oxygen (HBO) treatment is considered effective in reducing neuropsychiatric symptoms. This study aimed to analyze cognitive functions and WM diffusion properties in CO intoxication after standard HBO treatment. Seventeen CO intoxicated patients were evaluated 4-6 months after HBO treatment. They also underwent diffusion tensor imaging (DTI) and cognitive assessment, and the results were compared with those from 34 age-matched controls. DTI was transformed into fractional anisotropy (FA) and mean diffusivity (MD) and assessed at every voxel level with tract-based spatial statistics across the brain. Correlation between reduced FA and increased MD with neuropsychological deficits were performed. Cognitive results showed that impairment in executive function, as well as verbal and visual memories, were most prominent. There were extensive areas of increased MD and decreased FA. Correlation analyses showed that memory retrieval, judgment, and verbal generation tasks were related to FA of the frontotemporal WM. MD showed weaker correlation with cognitive deficits. These data suggest that neurologic deficits and WM changes are detectable 4-6 months after HBO therapy. The correlation of WM diffusion with cognitive deficits also suggests that reduced connectivity between different cortical regions is a pathophysiologic mechanism.