A 16-year-old male was admitted to our hospital because of fever, altered consciousness and subsequent tonic convulsions of upper and lower extremities. A head CT scan revealed evidence of diffuse brain edema. Novel influenza H1N1 viral RNA was detected in nasopharyngeal specimens by specific PCR examination. Oseltamivir, steroid pulse and intravenous immunoglobulin were administered without any effect. On day 3 after admission, the patient died of complications of DIC and multiple organ failure. Autopsy revealed neuropathological changes of the central nervous system, including congestion and marked edema of the brain. However, inflammatory cell infiltration in the meninges or brain parenchyma was not observed. Extensive disruption of astrocytic projections (clasmatodendrosis), which is indicative of acute encephalopathy, was detected by anti-glial fibrillary acidic protein (GFAP) immunostaining of brain tissue. This is the first autopsy case report of pandemic (H1N1) 2009 influenza virus-associated encephalopathy. The clinical course, laboratory profiles and pathological findings were similar to those of conventional seasonal influenza encephalopathy in children that are reported previously.