Neuromyelitis optica spectrum disorder (NMOSD) can coexist with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Patients with overlapping Aquaporin 4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD and anti-NMDAR encephalitis with positive NMDAR antibodies in the cerebrospinal fluid (CSF) are rare but should not be ignored. A unique case of NMOSD coexisting with anti-NMDAR encephalitis is presented. Case reports of AQP4-IgG-seropositive NMOSD overlapping with anti-NMDAR encephalitis with positive NMDAR antibodies in the CSF were reviewed. A 61-year-old female presented with headache, blurred vision, dysuria, limb weakness, coma, respiratory failure, and hypotension. Brain magnetic resonance imaging (MRI) showed abnormal signals in the left temporal lobe, white matter around the bilateral ventricles, midbrain, medulla oblongata, cervical, and upper thoracic medulla. AQP4-IgG antibodies were positive in the serum and CSF. NMDAR antibodies were positive in the CSF. The patient's condition was stable following intravenous gamma globulin, corticosteroids, immunosuppressants, and symptomatic support treatments. Only a single met the criteria of NMOSD simultaneously coexisting with anti-NMDAR encephalitis in addition to our own case. This case provides further evidence for the occurrence of NMOSD with AQP4-IgG-seropositive overlapping anti-NMDAR encephalitis in a Chinese patient. The mechanisms underlying the occurrence of double positive antibodies remains elusive. When NMOSD patients show unusual symptoms (abnormal behavior, prominent psychiatric manifestations, cognitive dysfunction, autonomic dysfunction), or atypical supratentorial lesions, the coexistence of anti-NMDAR encephalitis should be considered. Copyright © 2019. Published by Elsevier B.V.