A system for calculating cardiac output of a patient on an extracorporeal blood oxygenation circuit includes measuring first oxygenated blood flow rate by a pump in the extracorporeal circuit and a corresponding arterial oxygen saturation and recirculation in the extracorporeal circuit, then changing the pump flow rate, such as decreased, to produce a corresponding change in arterial oxygen saturation (wherein such change is outside of normal operating variances or drift), which change in the arterial oxygen saturation and recirculation are measured. From the first flow rate and the second flow rate along with the corresponding measured recirculation and the arterial oxygen saturation, the CO of the patient can be calculated, without reliance upon a measure of venous oxygen saturation. The system also includes an accommodation of oxygenation by the lungs of the patient during the extracorporeal blood oxygenation.