Although extracorporeal membrane oxygenation (ECMO) systems have been used to provide temporary support for patients with severe respiratory or cardiac failure, they are often bedridden, in part because of their bulky size which relies solely on an unlimited source of wall oxygen. However, there is an unmet clinical need for ambulatory ECMO which necessitates downsizing the ECMO system. We sought to develop a new oxygenator to reduce the dependence on the oxygen supply source. The proposed oxygenator features a dual-chamber gas exchangers, with one chamber primarily responsible for carbon dioxide removal using ambient air and a subsequent chamber primarily responsible for oxygen transfer using pure oxygen. Computational fluid dynamics was used to analyze the blood flow field to avoid adverse stagnation and optimize gas exchange performance. Bovine blood was used for in vitro gas transfer test. This new oxygenator demonstrated the capability to provide adequate respiratory support (both carbon dioxide removal and oxygen transfer) to adult patients at blood rate of 4–6 L/min with an oxygen supply of only 2 L/min. The reduced use of oxygen with this new oxygenator may pave the way for the development of potable ECMO systems.