Central vein thrombosis as a cause of chylothorax is uncommon, and in a few cases in the literature was related to thrombotic complications of central venous access devices (CVAD). Superior vena cava (SVC) occlusion-induced chylothorax has been described in adult sickle cell disease (SCD) in a setting of chronic indwelling CVAD. There are limited reports on chylothorax induced by central venous thrombosis secondary to chronic CVAD in children with SCD. We describe an 8-year-old male patient, with a history of SCD, maintained on long term erythrocytapheresis for primary prevention of stroke, and whose clinical course was complicated by chylothorax which was successfully treated with a pleuroperitoneal shunt.