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Premature infants may require packed red blood cell transfusions, but current guidelines lack empirical evidence and vary among institutions and prescribers.To compare the physiological changes in cardiovascular hemodynamics and oxygen delivery between premature infants with anemia who receive packed red blood cell transfusions and premature infants without anemia.The study was a prospective observational cohort investigation of 75 premature infants. Comparisons among the data were made before, during, and after transfusion in infants with anemia and over time in infants in the control group. In infants with anemia, feedings were withheld 12 hours before and after transfusions.Electrical cardiometry and near-infrared spectroscopy measurements in premature infants with anemia revealed changes in hemodynamic parameters not detected by standard bedside monitoring. Statistically significant changes were seen before and after transfusions in cardiac output, fractional tissue oxygen extraction, heart rate variability, heart rate complexity, and splanchnic regional tissue oxygen saturation.Bedside monitoring of cardiovascular hemodynamics and oxygen delivery during packed red blood cell transfusion may inform individualized care for the premature infant with anemia and could be useful for the development of evidence-based practice guidelines.