Both neuromyelitis optica spectrum disorder (NMOSD) and Wernicke's encephalopathy (WE) involve brain lesions. However, their treatments are quite different. In this report, we describe the case of a 29-year-old woman with NMOSD, who presented with clinical and imaging findings similar to those of WE. She was admitted to our hospital with a headache, vomiting, and loss of appetite for two weeks and diplopia for nine days. Magnetic resonance imaging revealed lesions in the area postrema, periaqueductal gray matter, thalamus, and right frontal lobe. Vitamin B1 supplementation was ineffective. The patient was diagnosed with NMOSD because serum aquaporin-4 antibody was detected after admission. Her symptoms improved with immunotherapy. The possibility of NMOSD should be considered in patients with suspected WE.