The purpose of this study was to assess how red blood cell (RBC) transfusions impact hemodynamic parameters in infants with single-ventricle lesions. This was a retrospective chart review. The setting was a pediatric cardiac intensive care unit at a tertiary care children's hospital. Fifty-nine patients <1 year of age with single-ventricle physiology who received a blood transfusion between December 2007 and April 2009 were analyzed. They received a total of 183 transfusions. Exclusion criteria included transfusions given within 72 h of cardiac surgery or transfusions given to patients with active bleeding. There were no interventions. The study population was divided into terciles based on pretransfusion hemoglobin (Hgb) concentration. The pretransfusion Hgb concentration in group A was 7.8 to 12.3 gm/dl, in group B was 12.4 to 13.2 gm/dl, and in group C was 13.3 to 15.7 gm/dl. Heart rate, blood pressure, arterial saturation, and cerebral near-infrared spectroscopy (cNIRS) values before transfusion, as well as at 1, 2, 4, 8, and 12 h after transfusion, were collected. There was significant improvement in diastolic blood pressure, arterial saturation, and cNIRS in group A after 12 h. Transfusions given in group B also resulted in improvement in diastolic blood pressure and arterial saturation, with less robust response of cNIRS. In group C, only arterial saturation values increased significantly. RBC transfusions can improve hemodynamics and markers of oxygen delivery in infants with single-ventricle physiology, but further studies are needed to determine an optimal Hgb level in this population. Interventions to increase Hgb above this level may be of limited benefit.