Human herpesvirus 6 infection is common after organ transplant. Generally, infection is asymptomatic or is associated with a mild illness. However, human herpesvirus 6 infection in these patients may as well be life threatening as a result of severe end-stage organ disease. Here, we have reported a case of a severe human herpesvirus 6 infection with cerebral, hepatic, and gastrointestinal involvement, which presented as intestinal pseudo-obstruction. The patient was a renal transplant recipient who was successfully treated with ganciclovir. We also reviewed the literature on human herpesvirus 6 diagnosis and the associated colitis and encephalitis with its infection in solid-organ transplant recipients.