Preterm infants often receive multiple packed red blood cell (PRBC) transfusions that are intended to improve tissue oxygen levels. Near-infrared spectroscopy (NIRS) monitors regional cerebral tissue oxygen saturation (CrSO(2)) and splanchnic tissue oxygen saturation (SrSO(2)). Before such technology can be employed in neonatal transfusion management, it must first be established that transfusions result in an increase in tissue oxygen saturation. This prospective, observational study used NIRS to determine if PRBC transfusions increase the CrSO(2) and SrSO(2) of symptomatic anemic premature neonates. CrSO(2) and SrSO(2) values were compared for 20-minute duration immediately before, during, immediately after, and 12 hours after transfusion. As a secondary objective, CrSO(2) and SrSO(2) values were correlated with hemoglobin (Hgb) levels. One-way analysis of variance and Pearson correlation statistical tests were used for analysis. A statistically significant increase in CrSO(2) and SrSO(2) values were observed after transfusion in the 30 subjects included (CrSO(2): 62.8 +/- 1.6, 65.6 +/- 1.7, 68.0 +/- 1.3, 67.6 +/- 1.4, P < 0.001 and SrSO(2): 41.3 +/- 2.2, 46.7 +/- 3.0, 52.1 +/- 2.8, 48.2 +/- 2.5, P < 0.001). No correlation was found between CrSO(2) or SrSO(2) and Hgb values. NIRS identified increases in CrSO(2) and SrSO(2) in preterm neonates after PRBC transfusions and has the potential to become incorporated into neonatal transfusion management paradigms.