Experiments to determine the effect of the oxygen-hemoglobin dissociation curve on oxygen delivery during neonatal anemia, were carried out on 15 sedated and ventilated lambs less than 48 hr of age. Eight of the animals were exchange transfused with adult blood. The P50 of the exchange transfused group was 32.1 mm Hg (low O2 affinity) compared to 19.4 mm Hg for the controls (high O2 affinity). The animals were made anemic by isovolumic exchange transfusions with plasma. At different levels of hemoglobulin defined as mild (8 mg/100 ml), moderate (6 mg/100 ml), and severe (4 mg/100 ml) anemia, tissue oxygenation, hemodynamic status, and blood gases were compared. Mixed venous PO2 was significantly lower in the high affinity group throughout this study. Cardiac output was significantly greater in the low affinity group during severe anemia. Oxygen consumption remained stable in the low affinity group, but decreased significantly in the high affinity group when the anemia was severe. The data indicate that during severe anemia, blood with a high P50 is more capable of adequately oxygenating tissues than that with a low P50.