A nine-year-old girl with Staphylococcus epidermidis meningitis combined with acute disseminated encephalomyelitis (ADEM) was enrolled in the present study, and exhibited sustained fever and headache for 5 days and a single seizure episode. Meningeal irritation and disturbance of consciousness were apparent. Cerebrospinal fluid examination revealed increased protein level and pleocytosis. Cerebrospinal fluid culture demonstrated Staphylococcus epidermidis growth. The patient was treated with intravenous cefotaxime, intravenous dexamethasone, and decreasing intracranial pressure for 3 weeks. Seizures and fever symptoms improved, but disturbance of consciousness, muscle weakness, and bilateral limb paresis were significant. IgG index was elevated and oligoclonal bands were positive in the cerebrospinal fluid. Magnetic resonance imaging demonstrated high T2-weighted signals in subcortical white matter, which were consistent with ADEM. High-dose methylprednisolone for 3 days and a 6-day pulse therapy with immunoglobulins resulted in improved clinical symptoms and cerebrospinal fluid examination. The patient’s temperature dropped to normal, and the headache disappeared. A Staphylococcus epidermidis infection associated with ADEM is uncommon in children. Results suggested that Staphylococcus epidermidis infection could be a pathogenic factor for ADEM, and ADEM is a complication of Staphylococcus epidermidis meningitis.