This review examines the role of extracorporeal membrane oxygenation (ECMO) in the management of severe acute respiratory distress syndrome (ARDS), emphasizing its contribution to lung-protective ventilation through optimizing oxygenation and ensuring optimal decarboxylation. Key determinants of oxygen delivery during ECMO include circuit blood flow, cannula size and positioning, and hemoglobin concentration. Strategies for troubleshooting oxygenation issues are reviewed, including recirculation, increased oxygen consumption, and oxygenator dysfunction. In contrast, carbon dioxide removal (decarboxylation), which ECMO circuits efficiently achieve, is primarily influenced by sweep gas flow and the patient’s systemic PaCO₂. Effective management of these factors is crucial to ensure optimal ECMO support, enable ultra-protective lung ventilation, and improve outcomes in critically ill patients with severe ARDS.