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Management of neonates with hypoplastic left heart syndrome following the Norwood procedure seeks to optimize systemic oxygen delivery while maintaining an appropriate distribution between systemic and pulmonary blood flow. The objective of this study was to quantify actively circulating blood volume, total cardiac output, the pulmonary-to-systemic blood flow ratio (Qp/Qs), and vascular resistance indices at fractions of inspired oxygen (FiO2) of 0.21, 0.5, and 0.9 during the early postoperative period. Measurements were obtained in 16 neonates using an ultrasound dilution technique that determines hemodynamic variables from changes in blood ultrasound velocity following injection of isotonic saline (COstatus, Transonic Systems Inc.). An increase in the Qp/Qs ratio was observed with rising FiO2, which was associated with a reduction in systemic blood flow, while pulmonary blood flow remained statistically unchanged across the FiO2 levels studied. This pattern is consistent with the interpretation that pulmonary blood flow in this setting is mainly influenced by the mechanical properties of the right ventricle to pulmonary artery shunt rather than by FiO2 mediated changes in pulmonary vascular tone. Actively circulating volume index was reduced at baseline and decreased further with increasing FiO2 accompanied by an increase in systemic vascular resistance. These findings indicate that the early postoperative hemodynamics in neonates after the Norwood procedure are more responsive to alterations in systemic circulation than to modulation of pulmonary vascular tone. Therapeutic strategies targeting augmentation of circulating blood volume and reduction of systemic afterload warrant further investigation as potential approaches to optimize postoperative management in this population.