Background: Perinatal hypoxic-ischemic brain injury remains a serious condition that causes significant mortality and long-term morbidity. It leads to a cascade of neurotoxic events involving energy failure and the accumulation of Reactive Oxygen Species (ROS). In the immature brain with its reduced capacity for defence against ROS, the resultant tissue damage may lead to severe neurological sequelae such as epilepsy and/or Cerebral Palsy (CP). Aim: was to investigate the association between Catalase (CAT) and Superoxide Dismutase (SOD2) genes polymorphisms and development of cerebral palsy in infants with Hypoxic-Ischemic Encephalopathy (HIE). Methods: This case control study included 100 children assigned to two equal groups: Group (I): Fifty patients with cerebral palsy due to (HIE) and Group (II): fifty healthy children as controls. Genomic DNA was extracted from venous blood and genotyped for SOD2 rs4880 and CAT rs1001179 using the process of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Results: The polymorphic CAT rs1001179 allele demonstrated a statistically significant association with the presence of CP (OR=2.249, 95%CI=1.311–3.859, P<0.05). Patients with at least one polymorphic CAT rs1001179 T allele were more prone to develop CP (P<0.05) compared to noncarriers. The investigated SOD2 rs4880 polymorphism was not significantly associated with the risk of CP (P=0.663). Conclusion: CAT rs1001179 polymorphism could be used to identify children who are more likely to develop CP after perinatal HIE.