Patients suffering from sickle cell disease show an increased ischemic intolerance due to continuous pro-inflammatory activation and dysfunction of the endothelium by recurrent vaso-occlusive episodes. The presented case shows the manifestation of a postoperative compartment syndrome of the lower leg following the intraoperative use of blood arrest in a patient with previously unknown sickle cell disease. Preexisting vulnerability for tissue hypoxia in patients at risk should be a major concern for intraoperative use of blood arrest during surgery of the extremities.