Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a recently identified syndrome characterized by psychosis and dysautonomia. Treatment includes resection of the underlying tumor. While the pathologic mechanism involves disruption of NMDA function by anti-NMDA receptor autoantibodies, there are few descriptions of the perioperative management or anesthetic approach for such patients. We report a classic presentation of anti-NMDA receptor encephalitis and describe the use of total IV anesthesia with NMDA receptor-sparing drugs. Modest postoperative analgesic requirements, not reported in prior cases, are also described in our report.