The ability to monitor the match between systemic oxygen delivery and consumption using mixed venous oxygen saturation is an important component of management of critically ill patients. Mixed venous oxygen saturation is a particularly useful parameter in circumstances where systemic oxygen delivery is significantly compromised, such as the acute respiratory distress syndrome. With the advent of venovenous extracorporeal life support (ECLS) in the treatment of this condition, however, accurate measurement of true mixed venous oxygen saturation has not been available, because of this artificial elevation of venous oxygen content. Using an algebraic solution, the authors developed an equation to calculate true patient mixed venous oxygen saturation during ECLS. This is accomplished using readily obtainable data such as cardiac output, ECLS flow, ECLS circuit pre and post oxygenator blood oxygen content, pulmonary arterial oxygen saturation, and patient hemoglobin. The formula has been used in an in vitro model, simulating venovenous ECLS and native venous saturation ranging from 20- 72%, with a resulting correlation coefficient between calculated and measured saturation of 0.983 and a y intercept of 0.7. Using this new mathematical model, previously unobtainable information about the match of oxygen delivery and consumption in venovenous ECLS is now available. This information will facilitate optimal management of oxygen kinetics in patients during venovenous extracorporeal support.