Central and peripheral nervous system infection due to cytomegalovirus (CMV) is extremely rare in immunocompetent patients. Here, we present an unusual case of a young immunocompetent African-American woman who developed a severe form of CMV encephalomyelitis and polyradiculitis with a prolonged and complicated hospital course. The patient was treated with a prolonged course of antiviral medications and showed some improvement in her symptoms. This unusual presentation adds to the limited literature on the diagnosis, treatment and prognosis of severe CMV infection in immunocompetent hosts.