Total hip arthroplasty (THA) performed in patients with osteonecrosis, caused by sickle cell disease, carries a higher risk of medical and orthopedic complications, than those observed after THA for osteonecrosis related to other conditions. We report such a case of a male patient, who underwent one-stage revision hip arthroplasty due to septic cup loosening after primary cementless THA and later developed severe septic osteomyelitis of the ipsilateral hemipelvis that had a fatal outcome. The relative literature regarding loosening and infection after THA in patients with sickle cell disease is thoroughly reviewed.