The most common cause of death among patients with SCD is acute chest syndrome (ACS), which is defined as the presence of a new pulmonary infiltrate on chest radiograph accompanied by chest pain, tachypnea, tachycardia, fever, hypoxia, crackles, and/or wheezes. Based on these diagnostic criteria, all of which were present in this patient, a diagnosis of ACS was made following her initial hypoxic event. The most common causes of ACS are fat embolism from bone marrow and infection with Chlamydia, mycoplasma, or viruses. The pathophysiology of ACS is believed to be related to the inability of injured lung tissue to reoxygenate sickled RBCs, thereby inducing activation of the endothelium, leading to aggregation of sickled cells in the pulmonary microvasculature, resulting in increased inflammation and lung infarction. Incentive spirometry has been shown to prevent the development of pulmonary complications in patients admitted with sickle cell disease and chest pain above the diaphragm. Therapeutic options for the treatment of ACS are rather limited and predominantly involve supportive care. The mainstay therapies are similar to those of vasoocclusive crisis and include cautious hydration, oxygen therapy, and pain control. Additionally, given the increased likelihood of concurrent pulmonary infection, antibiotics covering the aforementioned pathogens are indicated. Multiple studies have shown that blood transfusion can rapidly improve oxygenation and positively alter the course of the disease process. Exchange transfusion remains controversial; however, it is appropriate to consider in critically ill patients with deteriorating cardiopulmonary status because it may improve outcomes.