Acute chest syndrome (ACS), a vaso-occlusive crisis in patients with sickle cell anemia, is a lifethreatening condition and a leading cause of death in these patients. It is treated with analgesics, antibiotics, intravenous fluid, supplemental oxygen (or ventilatory support in severe cases) with simple or exchange transfusion, being the mainstay of therapy. We report a young Jehovah's Witness (JW) patient with sickle cell anemia who presented with ACS. Her religious beliefs precluded the use of blood products. Despite concomitant hemolytic and aplastic crisis and a hemoglobin nadir of 3.1 g/dL, the patient was treated successfully with supportive care-including mechanical ventilation, sedation, paralysis, and erythropoiesis stimulation-and survived. A maximal supportive strategy consisting of ventilatory support with a high fraction of inspired oxygen, sedation, paralysis, erythropoiesis stimulation, and limitation of blood draws can result in the successful treatment of JW patients who refuse blood products.