Sickle cell disease (SCD) is a hereditary haemoglobinopathy that results in polymerization of haemoglobin molecules and subsequent vaso-occlusion. A common cause of death in adults is acute chest syndrome (AChS) with resulting hypoxemic respiratory failure. Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has been used successfully in acutely reversible respiratory failure when conventional mechanical ventilation has been unable to adequately oxygenate and ventilate in a lung-protective fashion. We present an adult SCD patient with severe respiratory failure due to AChS, successfully treated with VV-ECMO. We also discuss some of the technical challenges and considerations when using ECMO in the SCD patient.