Mania is a rare clinical manifestation of delayed anoxic encephalopathy (DAE). Prior case reports on mania after hypoxic injury involved patients with a previous history of mania or depression, potentially reflecting a recurrence of premorbid mood disorders after hypoxia rather than pure secondary mania. Herein, we report a 55-year-old woman with no past history of neurological or psychiatric illness, who developed mania as a symptom of DAE after carbon monoxide intoxication. Brain magnetic resonance imaging showed diffuse white matter lesions, particularly visible in the frontal white matter. This frontal lesion may have prevented frontal inhibition from being transmitted to the basotemporal limbic area, resulting in mania manifested as a burst of limbic activity.