BACKGROUNDThis study examines the relationship between oxidative stress, anti-oxidative markers, and the Ala16Val SOD2 polymorphism in children with autism spectrum disorder (ASD) to better understand ASD severity and susceptibility.MATERIAL AND METHODSThe study included 80 children (40 with ASD and 40 controls) from Erbil City, Iraq.RESULTSSerum antioxidant markers, such as superoxide dismutase (SOD) and glutathione peroxidase (GPX), were significantly lower in ASD patients compared to controls (P = 0.036 and P < 0.001, respectively), while markers of oxidative damage, including malondialdehyde (MDA), nitric oxide (NO), and cytochrome C, were significantly elevated (P < 0.001). Regression analysis revealed reduced SOD and GPX activities were strongly associated with increased autism severity, as measured by the childhood autism rating scale (CARS), while elevated NO and cytochrome C levels also correlated positively with higher CARS scores. Although the Ala16Val SOD polymorphism was not significantly associated with ASD risk, logistic regression showed no connection between SOD genotypes and serum SOD levels.CONCLUSIONThese findings suggest oxidative stress and impaired antioxidant defense play critical roles in ASD severity.