In humans, the sole endogenous source of carbon monoxide is heme degradation. We report the development of prolonged carboxyhemoglobinemia in a critically ill mechanically ventilated patient who required massive transfusion because of retroperitoneal hemorrhage secondary to pheochromocytoma. After the transfusion of 27 U of packed red blood cells, the maximum carboxyhemoglobin level was 6.4%. Although ventilation was controlled with a fraction of inspired oxygen of 0.35–0.5 and external drainage of blood occurred, the concentration of carboxyhemoglobin remained at 1.7%–5.6% for days. Red blood cells for transfusion may be contaminated with carbon monoxide and may have carboxyhemoglobin levels of up to 12%; this may also have contributed to carboxyhemoglobinemia in our patient. If significantly increased concentrations of carboxyhemoglobin develop, therapy to decrease the concentration of carboxyhemoglobin (such as fraction of inspired oxygen of 1.0 and/or minute ventilation or hyperbaric oxygen) or removal of the source should be considered.