Cytomegalovirus (CMV) encephalitis most commonly occurs in patients with advanced human immunodeficiency virus infection and profound CD4 cell depletion and is rare in transplant recipients. We describe a patient with pathologically proven CMV ventriculoencephalitis that occurred after human herpesvirus-6 limbic encephalitis, following reduced-intensity conditioning cord blood transplantation (CBT). At approximately day 150 after CBT, the patient became acutely confused after steroid therapy for grade III acute graft-versus-host disease. Fluid-attenuated inversion recovery magnetic resonance imaging of the brain revealed a communicating hydrocephalus with abnormal periventricular hyperintensity. Neuropathologic examination of the brain at autopsy revealed necrotizing CMV ventriculoencephalitis, limbic encephalitis, and multifocal necrotizing leukoencephalopathy. This case represents the first report of CMV encephalitis following CBT and serves to highlight the interrelationship between viruses in transplant recipients.