Previous DTI cross-sectional studies have showed the cerebral damage feature was different in the three clinical stages after carbon monoxide poisoning. Diffusional kurtosis imaging (DKI) is an advanced diffusion imaging model and considered to better provide microstructural contrast in comparison with DTI parameters. The primary aim of this study was to assess microstructural changes in gray and white matter with diffusional kurtosis imaging in the acute, delayed neuropsychiatric, and chronic phases after acute carbon monoxide (CO) poisoning. The secondary aim was to relate diffusional kurtosis imaging measures to neuropsychiatric outcomes of acute carbon monoxide poisoning.In all, 17 patients with acute carbon monoxide poisoning and 30 sex- and age-matched healthy volunteers were enrolled in the study. Patients were scanned within 1 week, 3-8 weeks, and 6 months after acute carbon monoxide poisoning. Diffusional kurtosis imaging metrics including mean kurtosis, mean diffusivity, fractional anisotropy, and kurtosis fractional anisotropy were measured in 11 ROIs and then further correlated with neuropsychiatric scores.In WM, mean kurtosis tended to increase from the acute-to-delayed neuropsychiatric phases and then decrease in the chronic phase, while in GM mean kurtosis showed a constant decline. Contrary to mean kurtosis, mean diffusivity first decreased then tended to increase in WM, while in GM, from the acute to chronic phases, mean diffusivity showed a constant increase. In both WM and GM, the fractional anisotropy and kurtosis fractional anisotropy values progressively declined with time. Kurtosis fractional anisotropy showed the best diagnostic efficiency with an area under the curve of 0.812 ( = .000). Along with neuropsychiatric scores, kurtosis fractional anisotropy of the centrum semiovale and Digit Span Backward were most relevant ( = 0.476, = .000).Longitudinally, microstructural changes were inconsistent in WM and GM with time after acute carbon monoxide poisoning. Diffusional kurtosis imaging metrics provided important complementary information to quantify the damage to cognitive impairment.