A co-infection with Mycoplasma pneumoniae and cytomegalovirus (CMV) resulting in an acute demyelinating polyneuropathy is reported in an immunocompetent girl. Two months following a respiratory infection, the patient showed a symptomatology consisting of weakness in lower limbs, followed by facial asymmetry and arm weakness. Serum M. pneumoniae antibodies were elevated and active CMV infection was diagnosed by polymerase chain reaction (PCR) performed on cerebrospinal fluid. Treatment with oral clarithromycin, intravenous immunoglobulins and ganciclovir was associated with rapid improvement and complete recovery. It is very probable that clinical findings were secondary to the reactivation of CMV caused by persistent M. pneumoniae infection in the respiratory tract. This may be the first report in the pediatric literature of a co-infection of M. pneumoniae and CMV resulting in peripheral nervous system involvement.