A patient with an atypical presentation of herpes simplex virus (HSV) encephalitis mimicking acute cerebral infarction was reported. A 48-year-old man developed left-sided hemiparesis, convulsive seizures, and loss of consciousness. Brain magnetic resonance imaging revealed high intensity areas in the right frontal to parietal lobes on T2-weighted and diffusion-weighted images. Soon after admission with suspected cerebral infarction of the right middle cerebral artery region, the patient had high fever with frequent seizures and severe loss of consciousness. Laboratory findings including cerebrospinal fluid established a diagnosis of HSV encephalitis, and a state of apalic syndrome persisted despite aggressive antiviral therapy.