OBJECTIVE To study the MRI-based characteristics of acute carbon monoxide poisoning (ACOP) and delayed encephalopathy after acute carbon monoxide poisoning (DECAMP), and to compare the degree of brain damage. METHODS A retrospective analysis was performed on the clinical and MRI data of 27 patients diagnosed with ACOP and 35 patients diagnosed with DECAMP. Ten healthy volunteers were recruited in the normal control group. All subjects received both routine MRI and diffusion-weighted MRI. Apparent diffusion coefficient (ADC) was determined with symmetric measurement of region of interest in the bilateral globus pallidus, white matter around lateral ventricle, and centrum semiovale. ADC values were compared afterwards. RESULTS Thirteen of the 27 ACOP cases were found of symmetrical abnormal signal in the bilateral globus pallidus, among whom 8 patients only showed pallidum region involvement, while the other 5 patients showed involvement of other regions. Eight ACOP patients showed cortical and subcortical white matter involvement, and 4 cases showed diffused abnormal signal around the bilateral ventricles and in the bilateral centrum semiovale. Two cases of ACOP presented with multiple region involvement. Thirty-five DECAMP patients showed diffused swelling and symmetric demyelination in multiple regions of the brain parenchyma. The periventricular white matter and centrum semiovale were involved in 33 cases, the deep brain nuclei were involved in 23 cases, and the cerebral cortex was involved in 3 cases. The ACOP and DECAMP groups had significantly lower ADC values in the periventricular white matter and bilateral centrum semiovale than the normal control group (P < 0.05), and the ADC values were significantly lower in the DECAMP group than in the ACOP group (P < 0.05). The ACOP group had a significantly lower ADC value in the globus pallidus than the DECAMP group and normal control group (P < 0.05); the DECAMP group had a significantly higher ADC value in the globus pallidus than the ACOP group and normal control group (P < 0.05). CONCLUSION Routine MRI and ADC value can evaluate the degree of brain damage in ACOP and DECAMP patients based on lesion involvement on a more microscopic scale. It can provide valuable information for therapy selection and prognostic evaluation.