Background The influence of deep hypothermia with either circulatory arrest (DHCA) or low-flow (DHLF) perfusion on pulmonary surfactant metabolism in neonates undergoing cardiac surgery remains unknown. This study was conducted to determine the influence of either strategy on surfactant metabolism and pulmonary function with neonatal piglet model. Methods Sixteen piglets underwent 90-minute deep hypothermia, either with circulatory arrest or low-flow perfusion (30 mL · kg −1 · min −1) at 18°C. Disaturated phosphatidylcholine, total phospholipids, and total proteins from tracheal aspirates were measured serially until the end of cardiopulmonary bypass. Lung static compliance, airway resistance, and arterial blood oxygen partial pressure to inspired oxygen fraction were also measured. Results The DHLF caused more significant decrement of pulmonary static compliance than DHCA (3 ± 0.4 mL · cmH 2O −1 vs 3.5 ± 0.3 mL · cmH 2O −1 at 90 minutes of deep hypothermia). Arterial blood oxygen partial pressure to inspired oxygen fraction decreased more significantly after cardiopulmonary bypass in the DHLF group than the DHCA group (205 ± 84 mm Hg vs 302 ± 96 mm Hg). The DHLF caused more severe decrement of disaturated phosphatidylcholine total phospholipids (50% ± 21% vs 67% ± 23% of baseline at 90 minutes of deep hypothermia) and disaturated phosphatidylcholine total proteins (58% ± 23% vs 73% ± 23% of baseline at 90 minutes of deep hypothermia) than DHCA. More significant water retention developed in the lung in the DHLF group than in the DHCA group. The extent of surfactant depletion was statistically correlated with the extent of pulmonary functional deterioration in either group. Conclusions The DHCA induces less injury on pulmonary surfactant metabolism and pulmonary function than DHLF.