Patients with mitochondrial disease exhibit disrupted pyruvate oxidation, resulting in intraoperative and perioperative physiologic derangements. Increased enzymatic conversion of pyruvate via lactate dehydrogenase during periods of fasting or stress can lead to metabolic decompensation, with rapid development of fatal lactic acidosis. We describe the intraoperative management and postoperative critical care of a patient with mitochondrial disease who presented for repair of esophageal perforation following repair of a paraesophageal hernia. His surgery was complicated by the development of metabolic crisis and severe lactic acidosis which became resistant to conventional therapy before ultimately resolving with the initiation of venoarterial extracorporeal membrane oxygenation (VA-ECMO).