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To compare oxygen consumption (Vo2) measured by indirect calorimetry before and after a packed red blood cell (PRBC) transfusion in patients with isovolemic anemia.Prospective, repeated-measures clinical study.Outpatient pediatric hematology-oncology clinic.A total of 17 pediatric hematology-oncology outpatients undergoing a PRBC transfusion for a hematocrit of <26%.Vo2 was measured by indirect calorimetry before and after a PRBC transfusion.Baseline hematocrit averaged 23% (15.5–25.7%), hemoglobin averaged 8.24 g/dL (5.2 g/dL–9.3 g/dL). Patients received an average of 10.3 mL/kg (2.8–17.5 mL/kg) of PRBC. After PRBC transfusion, all patients had an increase in Vo2, with a mean increase of 35.09 mL·min−1·m−2 (5–75 mL·min−1·m−2) or 19% (3.1–52%; p < .001). No significant correlation was found between the pretransfusion hematocrit or the volume of red blood cells administered and the change in Vo2. No significant change was noted in systolic blood pressure or respiratory rate. There were 14 patients who had a decrease in heart rate after PRBC transfusion, and seven patients who demonstrated an increase in Vo2 of <10% were compared with patients with a ≥10% change. No significant difference was found in age, height, weight, initial hematocrit, or volume of red blood cells transfused between these two groups.A significant increase in Vo2 was noted after a red blood cell transfusion in pediatric patients with isovolemic anemia. These findings suggest that Vo2 was dependent on the supply of oxygen in this subset of pediatric patients. Responding to increased oxygen delivery by increasing Vo2 implies that these patients were functioning in a state of relative oxygen deficit and had made physiologic adaptive changes to function in this state.