Pertussis, becomes serious when refractory hypoxemia develops from hyperleukocytosis and pulmonary hypertension, especially in infants. Here, we present the case of a 2 monthsold infant with severe pertussis pneumonia and hyperleukocytosis. A double volume exchange transfusion (ET) was needed for cardiopulmonary insufficiency unresponsive to intensive care. Oxygenation gradually improved within 48 hours after the treatment. A high white blood cell count can be a predictor of death in infants with pertussis. We considered that clinical improvement was observed due to a reduction cluster of leukocytes and also toxins, because of pertussis is a toxin-releasing infection. The early use of ET may prevent fatal outcomes in infants with severe pertussis, who failed to respond to standard therapy.