Lung function abnormalities in patients with thalassemia major are various, complex and of different etiological background. The aim of this study is to evaluate the pulmonary function changes during both rest and integrated cardiopulmonary exercise in patients with thalassemia major and its implications on their clinico laboratory status. The study included 30 cases of thalassemia major with mean age of 18 13.34. Nineteen healthy subjects with mean age of 12.79 2.02 were enrolled as a control group. Routine laboratory tests as well as assessment of pulmonary function test during both rest and integrated cardiopulmonary exercise were performed for cases and controls. A significant reduction in FVC was observed in cases than in controls (p<0.05) and 70% of cases had FVC below the normal predicted value, 3.33% of cases showed a reduction in FEV1/ FVC below the predicted value. Functional capacity, anerobic threshold and O2 pulse were reduced in cases than controls (p<0.05). Restrictive pattern of pulmonary dysfunction is the predominant abnormality in thalassemics. Poor cardiopulmonary exercise performance occurs and is multifactorial. The integration of pulmonary function test in the scheduled follow up of thalassemics is highly recommended.