Rationale:Hypoglycemia may cause diverse neurological manifestations, ranging from focal neurological deficits to irreversible coma. Severe and persistent hypoglycemia can lead to hypoglycemic encephalopathy (HE). Imaging findings of HE at different stages of18F-FDG positron emission tomography/computed tomography (PET/CT) have rarely been reported. Herein, we describe a case of HE occurring in the medial frontal cortex, cerebellar cortex, and dentate nucleus using18F-FDG PET/CT images from different periods.18F-FDG PET/CT has a high value in displaying the lesion range and indicating the prognosis.Patient concerns:A 57-year-old male patient with type 2 diabetes (T2D) was transferred to the hospital with a history of unconsciousness for 1 night. The patient showed a significant decrease in blood glucose levels.Diagnoses:The patient was initially diagnosed with a hypoglycemic coma.Interventions:The patient subsequently underwent a comprehensive treatment. The18F-FDG PET/CT examination on the fifth day after admission revealed a significant symmetrical fluorodeoxyglucose (FDG)-positive accumulation in the bilateral medial frontal gyrus, cerebellar cortex, and dentate nucleus. A follow-up PET/CT examination 6 months later revealed hypometabolism in the bilateral medial frontal gyrus and no abnormalities in FDG uptake in the bilateral cerebellar cortex and dentate nucleus.Outcomes:The patient condition was stable 6 months later, with a slow response, memory deterioration, occasional dizziness, and episodes of hypoglycemia.Lessons:HE lesions with a high metabolic status may be related to a metabolic compensation mechanism in response to gray matter loss. Some of the more severely damaged cells eventually die even after the blood sugar levels return to normal. Less damaged nerve cells can be recovered.18F-FDG PET/CT has high value in indicating the lesion range and prognosis of HE.