The case of an obese patient who developed massive centrilobular liver cell necrosis, severe coagulopathy, acute renal failure, and encephalopathy is presented. Hypovolemia and heart failure were absent, but the acute liver disease was associated with severe arterial hypoxemia due to obstructive sleep apnea that was shown by the nocturnal blood oxygen desaturation, the results of the polysomnographic study, and normal baseline pulmonary function tests. In this obese patient, liver cell necrosis was caused by severe liver cell hypoxia secondary to severe arterial hypoxemia as a consequence of obstructive sleep apnea associated with a Pickwickian syndrome. This observation is consistent with the hypothesis that liver ischemia was directly related to severe arterial hypoxemia.