This study compared the effect of unprocessed and processed packed red blood cells (PRBCs) with the continuous autotransfusion system (CATS) during neonate heart surgery. Sixteen neonatal patients undergoing cardiac surgery were randomly divided into two groups: unprocessed PRBC (C group, n = 8); processed PRBC (P group, n = 8). The CATS was employed perioperatively. Series laboratory and clinical parameters, including levels of hematocrit, blood potassium, blood glucose, blood lactate, acid-base, and total priming volume of PRBC, were used to compare the effect between the two groups. Before CPB, the hematocrit of processed PRBCs in P group was significantly higher than those in C group (p < 0.01), and the concentrations of potassium, blood glucose, and lactate of processed PRBCs in P group were significantly lower than those in C group (p < 0.01). At the beginning and the end of CPB, the hematocrit levels in P group were all higher than those in C group (p < 0.05); lactate levels in P group were significantly lower than those in C group at the beginning of CPB (p < 0.01), and lower than that of C group at the end of CPB (p < 0.05). The total priming of PRBCs in P group was significantly less than that in C group (p < 0.01). Perioperative processing with CATS provided a high-quality RBC concentration, decreased the total priming of PRBCs, providing increased high-quality blood salvage during neonatal CPB procedure.