A system for calculating cardiac output (CO) of a patient undergoing veno-arterial extracorporeal oxygenation includes measuring first oxygenated blood flow rate by a pump in the extracorporeal blood oxygenation circuit as introduced into an arterial portion of the patient circulation system and a corresponding arterial oxygen saturation, then changing the pump flow rate, such as decreasing, to produce a corresponding change in arterial oxygen saturation (wherein such change is outside of normal operating variances, operating errors or drift), which change in the arterial oxygen saturation is measured. From the first flow rate and the second flow rate along with the corresponding measured arterial oxygen saturation, the CO of the patient can be calculated, without reliance upon a measure of venous oxygen saturation. Alternatively, the CO of the patient can be calculated, without reliance upon a change in flow rate by changing a gas exchange with the blood in the extracorporeal blood oxygenation circuit to impart corresponding changes in a blood parameter in the arterial portion of the patient circulation system and the blood delivered from the extracorporeal blood oxygenation circuit.
