The aim of this study is to evaluate the effect of temperature on cerebral oxygen metabolism at total body flow bypass and antegrade cerebral perfusion (ACP). Neonatal piglets were put on cardiopulmonary bypass (CPB) with the initial flow rate of 200 mL/kg/min. After cooling to 18°C (n = 6) or 25°C (n = 7), flow was reduced to 100 mL/kg/min (half-flow, HF) for 15 min and ACP was initiated at 40 mL/kg/min for 45 min. Following rewarming, animals were weaned from bypass and survived for 4 h. At baseline, HF, ACP, and 4 h post-CPB, cerebral blood flow (CBF) was measured using fluorescent microspheres. Cerebral oxygen extraction (CEO2) and cerebral metabolic rate of oxygen (CMRO2) were monitored. Regional cranial oxygen saturation (rSO2) was continuously recorded throughout the procedure using near-infrared spectroscopy. At 18°C, CBF trended lower at HF and ACP and matched baseline after CPB. CEO2 trended lower at HF and ACP, and trended higher after CPB compared with baseline. CMRO2 at ACP matched that at HF. Cranial rSO2 was significantly greater at HF and ACP (P < 0.001, P < 0.001) and matched baseline after CPB. At 25°C, CBF trended lower at HF, rebounded and trended higher at ACP, and matched baseline after CPB. CEO2 was equal at HF and ACP and trended higher after CPB compared with baseline. CMRO2 at ACP was greater than that at HF (P = 0.001). Cranial rSO2 was significantly greater at HF (P = 0.01), equal at ACP, and lower after CPB (P = 0.03). Lactate was significantly higher at all time points (P = 0.036, P < 0.001, and P < 0.001). ACP provided sufficient oxygen to the brain at a total body flow rate of 100 mL/kg/min at deep hypothermia. Although ACP provided minimum oxygenation to the brain which met the oxygen requirement, oxygen metabolism was altered during ACP at moderate hypothermia. ACP strategy at moderate hypothermia needs further investigation.