Sickle cell disease is an inherited disorder and individuals who are homozygous for the sickle cell gene (HbS/S) show the clinical manifestations of the disease. The individuals who are heterozygous for the sickle cell gene (HbA/S) are referred to as sickle cell trait. In these people, under normal circumstances, symptoms are usually absent or mild. However, thorough investigation of the latter condition is also important, because sickling could occur under certain situations, such as prolonged hypoxia. The level of haemoglobin S(HbS), the ratio of HbS to haemoglobin A (HbA) and the presence of variants such as haemoglobin C (HbC) can alter the entire course of the condition. An unexpected sudden death in a 41-year-old Nigerian, who was apparently in good health and was on a long duration flight, is presented. According to available evidence he was previously diagnosed to be suffering from sickle cell trait. Based on medical advice oxygen was supplied to him throughout the flight. Two hours prior to landing at the international airport in Kuala Lumpur, Malaysia he suddenly became breathless and died shortly after. Autopsy revealed that the immediate cause of death was pulmonary thrombo-embolism originating from calf vein thrombosis. It was also established that the thrombus in the calf vein was not pre-existing. Histology revealed that there was extensive and generalized sickling. Haemoglobin electrophoresis on the postmortem sample of blood confirmed that the deceased had Hb S/C disease and not sickle cell trait. The presence of HbC together with the long hours of flight and associated inactivity had probably complicated the case. Various aspects of the sickle-cell condition are highlighted. Allegations of negligence were made against the airline and the doctor who cleared the deceased in Nigeria (the deceased was employed in a well-known multinational company) for long distance non-stop air travel. Various medico-legal issues pertaining to the cause and mode of death, the importance of an accurate diagnosis of the precise sickling disorder and possible negligence on the part of various agencies are discussed.