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Orbital apex syndrome (OAS) manifests as multiple cranial nerve palsies caused by an abnormal nerve response to inflammation or other processes. Central diabetes insipidus (CDI) is characterized by deficient synthesis or secretion of antidiuretic hormone. A 62-year-old woman underwent myringotomy for otitis media with effusion. Two months after the procedure, symptoms of hearing loss had not improved, and she underwent left tympanoplasty and mastoidectomy. After surgery, she presented with left ocular pain and visual loss. Neurologic examination revealed ptosis, total ophthalmoplegia, and a relative afferent pupillary defect on the left eye. Magnetic resonance imaging showed an asymmetric contrast-enhancing lesion in the left orbital apex and left cavernous sinus, with adjacent dural thickening and enhancement. OAS was diagnosed, and steroid treatment was started. During the regular follow-up period, she reported polyuria, and CDI was diagnosed. Treatment with intranasal desmopressin 10 μg twice daily was started, and symptoms greatly improved. The mechanism underlying the association of CDI with OAS is unclear, and further research is needed. The present case suggests that polyuria in OAS should alert neurologists and ophthalmologists to possible CDI. (J Nippon Med Sch 2019; 86: 254 257)