Background: A pro-angiogenic state has been found in adults with sickle cell disease (SCD), mainly because of elevated angiopoietin-2 levels. Aim of the work was to determine the level of Angiopoietin-2 in children and adolecents with SCD and assess its relation to markers of hemolysis and iron overload. Methods: Forty SCD patients in steady state were studied focusing on hydroxyurea therapy, hematological profile and serum ferritin. Patients were compared to 40 healthy controls. Results: Angiopoietin-2 levels were significantly higher in SCD patients compared with healthy controls (8506.3 ± 3789.5 pg/mL versus 2791.7 ± 1263.6 pg/mL; p<0.001). Angiopoietin-2 levels were significantly higher in SCD patients with cardiopulmonary complications. Significant positive correlations were found between serum angiopoietin-2 levels and age as well as HbS. Conclusions: Elevated angiopietin-2 levels in SCD highlights the role of angiogenesis in the pathophysiology of SCD. Angiopoietin-2 may be considered a promising risk marker for screening of SCD patients at risk of cardiopulmonary complications.