Performing cardiac surgery on pediatric Jehovah's Witness patients is a great challenge for the surgical team and especially for the perfusionist. Jehovah's Witnesses reject blood transfusions on the grounds of their literal interpretation of passages of the Bible. In accordance with this belief, Jehovah's Witnesses feel that it is also forbidden to retransfuse autologous blood that has been separated from their own circulatory system. We report the use of cardiopulmonary bypass (CPB) during open-heart surgery in three infants with a body weight of 4.5 kg, 3.5 kg, and 3.1 kg, respectively, without transfusion of blood components. A small-volume CPB circuit with a priming volume of 200 mL, including the arterial line filter, was designed to decrease the degree of hemodilution. A dedicated pediatric heart lung machine console with remote pump heads and intensive blood conservation efforts allowed the operation without the use of donor blood. The CPB circuits were primed with crystalloid solution only. The procedures were performed in normothermia or in moderate hypothermia. Pre-CPB hemoglobin levels were 10.8 g/dL, 10.6 g/dL, and 8.5 g/dL. The hemoglobin concentrations measured during CPB ranged from 5.9 to 6.5 g/dL, 6.4 to 6.8 g/dL, and 5.5 to 5.9 g/dL, respectively. The patients did not receive any blood or blood products during their entire hospital stay.