EBV can produce a broad range of CNS disorders such as demyelinative diseases, acute encephalitis, cerebellar ataxia, myelitis, or meningitis. The role of EBV itself in acute encephalitis is not completely clear. Presently we described a 4 years old boy with EBV encephalitis that deceased after respiratory distress and cardio-respiratory arrest. At autopsy the most important changes in the brain were focal sub cortical peri-vascular mononuclear inflammation of the cerebral vessels. EBV antigens were demonstrated by immunohistochemistry in some cells of the vascular walls and in some glial cells of the brain. As expected this indicates a predominantly cellular response in the brain. The presence of EBV antigens by immunohistochemistry associated to a scarce inflammatory infiltrate supports the hypothesis that EBV itself plays a major role in the pathogenesis of EBV encephalitis.