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During regional anesthesia for carotid endarterectomy (CEA), 10% to 15% of patients develop signs of cerebral hypoxia after cross-clamping, manifested as changes in speech, cerebration or contralateral motor power. Reversal of such neurological deficits using administration of 100% O2 has been described. We used near-infrared cerebral oximetry to assess whether 100% O2 reliably improves regional cerebral oxygenation (rSO2) during carotid cross-clamping.Sixteen patients undergoing awake CEA were studied. Bilateral rSO2 optodes were applied before the initiation of sedation and the conduct of the regional blockade. Patients received 28% oxygen by Venturi facemask. Perioperative blood pressure was maintained at or within 10% above the patient’s normal limits during carotid cross-clamping. After cross-clamping, 100% O2 was administered for 5 min by a close-fitting anesthetic facemask. The O2 mask was then removed and the patient breathed room air. The effects on rSO2 readings and arterial blood gases were observed after each intervention.Data were analyzed for 15 patients. Ipsilateral rSO2 values decreased by 7.4% ± 5% after carotid cross-clamping. Administration of 100% O2 resulted in an increase in ipsilateral rSO2 in all patients of 6.9% ± 3.3% (range, 1%–12%) (paired t-test, P < 0.001) over the cross-clamped value while receiving 28% O2. Hemodynamic variables and arterial Paco2 values were unaltered.With the carotid cross-clamped, ipsilateral rSO2 was reliably increased by the administration of 100% O2 compared with 28% O2. The etiology of this increase is unclear, but may relate to the associated increase in O2 content of the blood or to an improvement in cerebral blood flow. Thus administration of 100% O2 during carotid cross-clamping may be beneficial for all patients undergoing CEA.