Human metapneumovirus (hMPV) is an emerging pathogen well known to cause respiratory tract infections in children and adults. It is responsible for approximately 5% to 10% of all hospitalizations of children due to acute respiratory tract infections. The hMPV can cause severe illness in children, immunocompromised persons, and the elderly, which can progress to severe respiratory failure requiring hospitalization and mechanical ventilation. Transmission occurs via contact with contaminated respiratory secretions (droplet, aerosol). The hMPV is rarely known to cause central nervous system complications. Descriptions of this syndrome are limited to case reports, most of which have been in children. Reports suggest that this virus has been linked to diseases of the central nervous system including acute encephalopathy, encephalitis, and febrile seizures. Review of the literature revealed only one confirmed case of hMPV isolated from the cerebrospinal fluid of a patient with concurrent encephalitis. We describe an adult patient with acute meningoencephalitis associated with hMPV, in whom a respiratory virus panel with polymerase chain reaction was positive for hMPV on nasopharyngeal swab, but was negative on the cerebrospinal fluid specimen.