Recent reports have documented human herpesvirus 6 (HHV-6) as a cause of high fever, bone marrow depression, and rash in liver transplant recipients in the absence of another known pathogen. We describe a 49-year-old liver transplant recipient who developed confusion, occipital headache, and involuntary movements of the limbs 3 weeks after orthotopic liver transplantation. HHV-6 was detected in the peripheral blood using a rapid culture assay. Examination of cerebrospinal fluid by polymerase chain reaction for HHV-6 was also positive. No other pathogens were identified. The patient improved after commencement of intravenous ganciclovir therapy. This case suggests HHV-6 needs to be considered in the differential diagnosis of unexplained confusion in liver transplant recipients.