Treatment of infected total knee arthroplasty requires aggressive management to treat the infection and restore joint function. For patients with infected knee arthroplasties, a two-stage procedure is used that involves resection of the joint and placement of an antibiotic impregnated cement spacer followed by implantation of a new prosthetic 6 weeks later. Patients undergoing the two-stage procedure typically endure high allogeneic blood transfusion rates (82% to 88%) and progressive anemia because the two surgeries are spaced closely and because the infection precludes the use of alternatives to allogeneic blood. Records were reviewed of 75 patients who underwent two-stage total knee arthroplasty to characterize perioperative hemoglobin levels and blood transfusion needs in this patient group. Although transfusions were administered only when warranted by clinical symptoms and were not based on predetermined hematologic values, 62 (82%) patients received a mean of 2.3 units of blood at first-stage surgery, and 60 (80%) patients received a mean of 2.1 units of blood at the second stage. Overall, only 12% of patients did not have allogeneic blood transfusion. At the first stage before resection, mean hemoglobin concentration was 11.6 g/dL and reached a mean nadir of 8.6 g/dL 3 days after surgery. At the second stage before reimplantation, hemoglobin concentration averaged 11.1 g/dL and reached a mean nadir of 8.2 g/dL 3 days after surgery. After the first stage, allogeneic blood transfusion failed to improve postoperative hemoglobin levels enough to prevent transfusions associated with the second-stage. Patients undergoing two-stage total knee arthroplasty have anemia, and a substantial proportion of these patients require allogeneic blood transfusion at both stages. Thus, novel blood management practices are required to improve hemoglobin levels and reduce allogeneic transfusion rates in this patient population.