Exposure to pesticides has been linked to an elevated risk of leukemia. The present research aimed to evaluate the relationship between organochlorine (OC) pesticides and biomarkers of oxidative stress in leukemia patients. This work was conducted on 109 patients with leukemia and 109 healthy controls. The serum concentrations of seven derivatives of OCs including alpha-HCH, beta-HCH, gamma-HCH, 2,4-DDT, 4,4-DDT, 2,4-DDE, and 4,4-DDE along with acetylcholinesterase (AChE), glutathione peroxidase (GPx), superoxide dismutase (SOD), paraoxonase-1 (PON1), and catalase (CAT) activities as well as total antioxidant capacity (TAC), nitric oxide (NO), protein carbonyl (PC), and malondialdehyde (MDA) levels were measured in all the subjects. Levels of OCs were remarkably higher in leukemia patients compared to the controls (p < 0.05). In addition, levels of SOD, AChE, GPx, PON-1, and TAC were remarkably lower in leukemia patients compared to controls (p < 0.05). In contrast, MDA, NO, and PC concentrations were higher in leukemia patients than in the controls (p < 0.05). Moreover, the serum level of 4,4-DDE was negatively associated with GPx activity (p = 0.038). Our findings suggest that OCs may play a role in the development of leukemia by disrupting the oxidant/antioxidant balance.