Despite reductions in surgical mortality, neurologic sequelae remain a devastating complication after cardiac surgery with cardiopulmonary bypass. Neurologic complications may be induced by a massive air embolism during cardiopulmonary bypass, even with extensive monitoring. This report describes a patient who had a fatal cerebral infarct during aortic valve and ascending aorta replacement surgery. We monitored jugular venous O₂ saturation (SjvO₂) and cerebral oximetry using near-infrared spectroscopy in the perioperative period. The operation and anesthesia were uneventful until the deep hypothermic total arrest for the replacement of the ascending aorta. However, restarting the cardiopulmonary bypass after deep hypothermic total arrest produced a brief (less than 10 seconds) but large amount of air in the root cannula. At this time, although cerebral oximetry did not show any changes, the SjvO₂ decreased to 21% for about 3 minutes and then normalized. At 8 hours after surgery, the patient showed seizures and severe edema in both cerebral hemispheres on the MRI. The patient died 21 days after surgery.