The most prevalent genetic disease in Africa and sub-Saharan Africa is sickle cell disease. Crisis often leads to severe pain in the limbs and chest region accompanied by oxygen deprivation to tissues. In children and adults, acute chest syndrome (ACS) which is a complication of vaso-occlusive crisis (VOC), is a life-threatening condition. A 24-year-old female with known Sickle Cell Disease (SCD) complained of generalized diffuse chest pains and was administered diclofenac at a peripheral hospital. The pains subsided. However, the condition relapsed and at another clinic, she was treated with i.v. paracetamol, morphine, pethidine, and i.v. fluids. Three (3) days had already gone by since the crisis started before a further transfer was made to the Greater Accra Regional Hospital. On arrival, she was diagnosed with chest and leg pains, shortness of breath, and VOC. Chest x-ray demonstrated patchy consolidation, infiltrates bilaterally, with right atrial enlargement. Clexane 80 mg BD, i.v. Omeprazole 40 mg b.d., Azithromycin tablets 500 mg, morphine syrup 10 mg/5 mL, Injection Rocephin 2 g, and infusion paracetamol 1 g were administered, followed by a continuous treatment review plan. Oxygen saturation was however generally constant at 99%. On day five (post admission-D5) the patient was moaning and restless. Her WBC started increasing [5.9-10.1 × 10³/μL (D5-D9)], platelets were still low (45 × 10³/μL), with Hb showing signs of fluctuations [6.3-9.0 g/dL (D2-D9)]. Blood culture results showed Gram-positive bacillus. Acute phase reactants, CRP (103.65 mg/dL) and ferritin (741.3 μg/L) were very high. RBC exchange transfusion by apheresis commenced at 10 pm (for 3 h). By 6 am the following day, the patient was described as having a calm night. Further drug modifications were made and by day 9 (D9) patient was only on Cap Omeprazole 20 mg once for 5 days, and tab dexamethasone 6 mg daily. The patient was discharged on day 11 post admission. Thus, from the onset of the crisis to the application of apheresis, 8 days had elapsed. However, five (5) hours after the RBC exchange transfusion by apheresis, pains subsided considerably. The key clinical message is that prompt resolution of ACS by therapeutic apheresis application will subsequently reduce the long-term pulmonary complications in SCD patients, hospitalization time, the overall financial burden, anxiety, and discomfort to patient and family.