Herpes simplex virus encephalitis (HSVE) is the most common cause of encephalitis with very high rates of mortality. Only 40 cases of postoperative HSVE have been reported; most authors agree it might be reactivation secondary to surgical stress and preoperative steroid immunosuppression. Concomitant HSVE and anti N-methyl-D-aspartate (NMDA) receptor, has already been reported. We report the first case of anti-NMDA receptor encephalitis after postoperative HSVE. Anti-NMDA receptor autoimmune encephalitis after postoperative HSVE is a cytokine-mediated encephalitis. Timely diagnosis and management of both conditions are of paramount importance for neurologic prognosis. Our case responded adequately after timely management with antiviral drug and immunotherapy.