We report a case of severe unilateral temporal lobe hypometabolism depicted on interictal FDG-PET/CT in a 56-year-old man presenting with cognitive-behavioral problems, affective disorder, receptive aphasia, and complex partial seizures. The seizures had been treated with gabapentin and phenytoin for 18 years. The extent and severity of hypometabolism were significantly greater than typically seen in patients with idiopathic temporal lobe epilepsy. The combination of electroencephalography, left temporal lobe encephalomalacia depicted on serial MRI, and the interictal FDG-PET findings implicated the temporal lobe as the site of seizure origin. Further clinical history disclosed a diagnosis of remote herpes simplex encephalitis (HSE) infection more than 24 years earlier confirmed by laboratory testing. The patient had been treated with antiviral therapy with full immediate neurologic recovery. Brain SPECT imaging has been previously reported in the literature to demonstrate focally increased cortical perfusion in acute HSE, followed by hypoperfusion of the affected region, in the recovery phase (between 3 and 6 months). A previous report of the FDG-PET findings in HSE showed hippocampal hypermetabolism acutely, then hypometabolism at 3 and 9 months. Our case provides evidence that the metabolic sequelae of HSE can become persistent, despite antiviral treatment, likely the result of gliosis and atrophy.