The current studies aimed at determining physical fitness indices and anthropometrics profiles of children with sickle cell anemia (SCA) after the use of hydroxyurea (HU). Ninety-three male schoolchildren--who participated previously in a similar study before the introduction of HU--comprising 2 groups participated in the studies. Group 1 was 41 children who were suffering from sickle cell disease (SCD) and were on HU for a minimum of 2 years, whereas group 2 was 50 normal healthy controls. Anthropometrics measurement and parameters of physical fitness were assessed in all subjects. All children were also subjected to a minimum of 6-minute running exercise test on a flat motorized treadmill at speed corresponding to 5 km/h. Throughout the test heart rate was monitored and recorded during exercise and for 10 minutes during recovery. Blood hemoglobin (Hb) and HbF% were measured after the use of HU. The mean values of weight, height, and lean body mass were still lower in the SCD children (P < .05) compared with the healthy subjects. However, they had significant decrease in the mean heart rate values and they spent longer time on the treadmill before they got tired compared to their previous performance and were just below the normal controls. Hydroxyurea treatment improved the aerobic exercise tolerance and most of the physical fitness parameters in children with SCD.