Background: Coronavirus disease MESHD 2019 (COVID-19) caused by SARS-CoV-2 has become a global pandemic, and those developing critically ill conditions have been reported to have mortality in the range of 39% to 61%. Due to the lack of definitive treatments, mechanical ventilation and supportive oxygenation therapy are key management strategies for the survival of patients with acute respiratory distress HP syndrome MESHD (ARDS). Optimizing oxygenation therapy is mandatory to treat patients with severe respiratory failure HP, to sufficiently compensate for the oxygen (O2) demand. We experienced a case of severe ARDS due to COVID-19 successfully treated with extracorporeal membrane oxygenation (ECMO) after increasing oxygen delivery according to O2 consumption measurement by indirect calorimetryCase Presentation: A 29-year-old obese but otherwise healthy man was hospitalized for treatment of COVID-19 pneumonia MESHD pneumonia HP presenting with a 4-day history of persisting cough MESHD cough HP, high fever MESHD fever HP, and dyspnea MESHD dyspnea HP. Mechanical ventilation, nitric oxide inhalation, and prone positioning were initiated in the ICU against severe respiratory dysfunction. Indirect calorimetry on the 3rd and 6th ICU days revealed persistent elevation of oxygen consumption (VO2) of 380 mL/min. Veno-venous ECMO was initiated on the 7th ICU day after further deterioration of respiratory failure HP. Periodic events of SpO2 decline due to effortful breathing was not resolved by neuromuscular blockade in attempt to reduce O2 consumption. Increasing the ECMO flow induced hemolysis MESHD and hyperkalemia MESHD hyperkalemia HP despite the use of large bore cannulas and ECMO circuit free of clots and defects. The hemoglobin management level was elevated from 10 g/dL to 13 g/dL to increase blood SERO oxygen capacity, enabling the reduction of ECMO flow while attenuating respiratory effort and maintaining SpO2. Lung protective ventilation strategy and prone positioning were continued for successful weaning from ECMO on the 16th ICU day, and the ventilator on the 18th ICU day.Conclusion: The present case of severe ARDS due to COVID-19 was successfully treated with ECMO. Enhancing oxygen delivery was crucial to compensate for the elevated O2 demand. Measuring O2 consumption by indirect calorimetry can elucidate the oxygen demand for optimizing the oxygenation therapy for successful management and survival of critically ill COVID-19 patients.