To elucidate the still unclear mechanism of delayed encephalopathy after carbon monoxide (CO) poisoning, we serially performed single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) and diffusion tensor imaging (DTI) on a 3.0T system and intelligence tests in 2 patients, while they were undergoing hyperbaric oxygenation therapy. The chronological changes in (1)H-MRS- and DTI-derived parameters indicated the following: (1) White matter demyelination, aerobic metabolism inhibition, and cytotoxic edema persisted for at least 3 months even after starting the hyperbaric oxygenation therapy; (2) the axonal function and structural integrity of the white matter were initially severely impaired and then gradually and partially improved for 5 months, showing changes similar to those in the scores of the intelligence tests. The results demonstrated that brain damage after CO poisoning may persist longer than expected, and that the (1)H-MRS- and DTI-derived parameters are good indicators of the clinical progress of a patient. The combination of (1)H-MRS and DTI on a 3.0T system is useful for monitoring the changes in brain damage and the clinical symptoms of patients with delayed encephalopathy after CO poisoning.