Background: Arylesterase activity of Paraoxonase-1 (ARE-PON-1) exhibits an antioxidant role which protects lipoprotein from oxidation. It is known that ARE-PON-1 antioxidant activity associated with high density lipoprotein cholesterol (HDL-C) reduces the oxidative damage mediated by low density lipoprotein cholesterol (LDL-C). The present study was aimed to examine the level of serum ARE-PON1 in Iraqi patients with β-thalassemia minor and its relationship with lipid profile (total cholesterol (TC), HDL-C, very low density lipoprotein (VLDL-C), and LDL-C) and hematologic changes as a part of antioxidant system action. Methods: In the present study, the ARE-PON-1 activity was investigated in serum of patients with β-thalassemia minor. Results: It has been revealed that the ARE-PON-1 activity was significantly decreased (P>0.0001) in patients group compared to healthy group. This was associated with slight decrease in the lipid profile of patient group (HDL, LDL-C, very low density lipoprotein cholesterol (VLDL-C), and total cholesterol (TC), except of triglyceride (TG) which showed a significant decrease (P>0.0001) compared to healthy group). Also, hematologic changes were investigated and showed depleting in most of white blood cell (WBC) and red blood cell (RBC) components. Conclusion: Patients with β-thalassemia minor are suffering from weakness in the antioxidant defence system expressed by dropping in the ARE-PON1 level and lipid profile that stimulate oxidation of many cell particles such as HGB, promote EOS apoptosis and rise of CD risk development.