Rapid reductions in P a CO 2 during extracorporeal membrane oxygenation (ECMO) are associated with poor neurologic outcomes. Understanding what factors determine P a CO 2 may allow a gradual reduction, potentially improving neurologic outcome. A simple and intuitive arithmetic expression was developed, to describe the interactions between the major factors determining P a CO 2 during venovenous ECMO. This expression was tested using a wide range of input parameters from clinically feasible scenarios. The difference between P a CO 2 predicted by the arithmetic equation and P a CO 2 predicted by a more robust and complex in-silico mathematical model, was <10 mm Hg for more than 95% of the scenarios tested. With no CO 2 in the sweep gas, P a CO 2 is proportional to metabolic CO 2 production and inversely proportional to the "total effective expired ventilation" (sum of alveolar ventilation and oxygenator ventilation). Extracorporeal blood flow has a small effect on P a CO 2 , which becomes more important at low blood flows and high recirculation fractions. With CO 2 in the sweep gas, the increase in P a CO 2 is proportional to the concentration of CO 2 administered. P a CO 2 also depends on the fraction of the total effective expired ventilation provided via the oxygenator. This relationship offers a simple intervention to control P a CO 2 using titration of CO 2 in the sweep gas.