Objective—To assess the physiologic response to, and acute survival of, cats undergoing cardiopulmonary bypass (CPB) and to evaluate the efficacy of a commercial human pediatric oxygenator system on cats weighing less than 6 kg.Study design—Experimental study.Animals—Six intact male catsMethods—Cats were placed on cardiopulmonary bypass by cannulating the cranial and caudal vena cavae and the carotid artery. The pediatric CPB circuit was primed with 150 mL of a balanced crystalloid solution. Venous drainage was enhanced by a controlled, vacuum‐assist system. A cross‐clamp was placed on the ascending aorta and cardiac arrest was induced by antegrade infusion of a cold cardioplegia solution. After 45 minutes of arrest time, the cross‐clamp was removed and the cats were weaned off bypass and decannulated. No blood products were administered. Heart rate, mean arterial pressure (MAP), central venous pressure, arterial blood gas, hematocrit (HCT), total plasma protein concentration (TP), serum electrolyte concentrations, and activated clotting time (ACT) were measured at baseline period (BL), during CPB, 60 minutes after CPB (CPB 60) and 90 minutes after CPB (CPB 90). A complete blood count (CBC), blood chemistry profile, and urinalysis were performed at BL, during CPB, and CPB 90. Cats were euthanatized after CPB 90.Results—Cardiopulmonary bypass resulted in a significant (P< .05) decrease in mean HCT (18.0%) and TP (2.3 gm/dL) at CPB 90 when compared to BL (30.5% and 6.0 gm/dL, respectively). The MAP at CPB 90 (54 mm Hg) was decreased from BL (94 mm Hg). The ACT increased from a mean of 124 seconds to > 400 seconds with heparinization and was reversed to 300 seconds with protamine. Mean platelet counts decreased from BL (369,000 /uL) to CPB 90 (94,500 /uL). Mean white blood cell counts decreased from 13,200 /uL at BL to 2,200 /uL at CPB 90. Upon reperfusion, 1 cat fibrillated but was successfully defibrillated.Conclusions—Cardiopulmonary bypass was performed successfully in 6 cats weighing less than 6 kg. Acute survival to 90 minutes after CPB was achieved in all 6 catsClinical relevance—The ability to perform CPB in the cat may allow intracardiac repair of various heart defects in this species.