In patients with acquired immune deficiency syndrome (AIDS), hypoosmolality is frequently observed, whereas hypernatremia is distinctly rare. We report two patients with advanced AIDS and cytomegalovirus (CMV) encephalitis, who developed severe hypernatremia without any thirst sensation, that is, adipsic hypernatremia. Both developed severe hypernatremia of up to 164 and 162 mmol/L, with serum osmolalities of 358 and 344 mOsmol/kg while remaining alert and denying thirst. Serum antidiuretic hormone (ADH) levels were 0.9 and 1.5 pg/mL, inappropriately low for the concomitant serum osmolalities. Vital signs were stable. During hypernatremia, urine osmolalities were 327 and 340 mOsmol/kg, and urine Na+ levels were 56 and 119 mmol/L, respectively. Periventricular white matter lesions were seen on cerebral nuclear magnetic resonance imaging (NMRI) in case 1, but the pituitary appeared normal in both cases. Survival after onset of hypernatremia was 6 and 4 weeks, respectively. Autopsy in case 1 showed typical findings of CMV encephalitis but normal pituitary, confirming that infection with HIV or CMV most likely caused the dysfunction of the central osmostat.