A 12-year-old White female with a history of sickle cell trait (HbAS), splenectomy, frequent pain crises, infections, and acute chest syndrome (ACS) presented to the emergency department (ED) with complaints of severe back and leg pain. She was administered morphine for her pain and was discharged upon improvement. Within 24 h, she returned to the ED with labored breathing, chest tightness, and pain. At this presentation, her physical examination was significant for tachypnea and tachycardia with sinus rhythm. A chest X-ray revealed infiltrates in her lower pulmonary lobes and she was diagnosed with severe ACS. She was administered morphine, fluids, ceftriaxone, ondansetron, and oxygen (2 L/min). While in the ED, she acutely decompensated, with increased oxygen requirement (2 to 4 L/min), became febrile, and experienced intensifying pain. A complete blood count (CBC) was performed and revealed leukocytosis, decreased red cell count, increased reticulocyte count, and normocytic, normochromic anemia (Table 1). Her peripheral blood smear also revealed moderate anisopoikilocytosis, scattered macrocytes, codocytes, sickle cells, and rare nucleated red blood cells. Her total bilirubin was increased (1.2 mg/dL; reference interval 0.1 to 0.7 mg/dL); however, no other markers of hemolysis were measured. Based on her clinical history, presentation, and abnormal CBC findings, hemoglobin (Hb) analysis was ordered to confirm her reported carrier status of HbAS. The Hb analysis was performed on a HPLC BioRad Variant β-thal Short Program and showed 54.3% hemoglobin A (HbA), 38% hemoglobin S (HbS), 3.8% hemoglobin A2 (HbA2), and 3.9% hemoglobin F (HbF). These results prompted the care team to reach out to the clinical laboratory to discuss the case in further detail.