Delivery of oxygen to the mitochondrium is a process involving multiple steps. We here present the integration of the mechanisms of oxygen delivery (DO ) during veno-venous (V-V) extracorporal membrane oxygenation (ECMO) into a holistic physiological model. The final steps of oxygen transport in this model are the convective transport of oxygen bound to hemoglobin in the arterial blood and the diffusion to the mitochondrium from the microcirculation. Limitation of DO may occur on both steps. In cases of severe respiratory failure without lung function, ECMO may provide the entire oxygen supply for the patients. If the cardiac output (CO) is significantly higher than the maximal ECMO flow, the addition of deoxygenated venous blood will lead to a low arterial oxygen saturation (SaO ). In this situation the convective transport of oxygen is mostly limited by the maximal ECMO flow. If a bi-caval dual lumen cannula is used, the recirculation may be very low. Lowering the CO in this situation will increase the arterial SaO . An increased arterial SaO may increase the oxygen transport to the mitochondrium by diffusion. The hypothesis derived from this model is that lowering the CO during V-V ECMO support in the situation described above might increase DO to the tissues by improving oxygen diffusion.