ObjectiveIn pregnancy, reducing inflammation and oxidative stress is important. Administration of melatonin during pregnancy can improve reproductive performance by improving the placental antioxidant system and inflammatory response. This investigation was carried out to evaluate the beneficial impact of melatonin on the oxidative stress state among high-risk pregnant women receiving enoxaparin and aspirin.MethodsIn this double-blind, placebo-controlled trial, 40 pregnant women, aged 15–45 years at 6 weeks of pregnancy, were randomly selected and divided into intervention and control groups. The control group received prophylaxis enoxaparin and aspirin once daily between 6 and 16 weeks of pregnancy. The intervention group was taken enoxaparin and aspirin for 9 weeks and melatonin once daily from the sixth week of pregnancy to delivery time. Blood samples were taken to measure some oxidative stress biomarkers including total antioxidant capacity (TAC), malondialdehyde (MDA), total thiol (T-SH), protein carbonyl (PCO), and nitric oxide (NO). The level of high-sensitivity C-reactive protein (hs-CRP) was also determined.ResultsTAC and T-SH levels increased significantly in the intervention group in comparison with the control group. Melatonin administration compared to the control group led to a significantly decreased level of NO and an insignificant hs-CRP level.ConclusionMelatonin supplementation in high-risk pregnancy had favorable effects on TAC, T-SH, NO, and hs-CRP levels, improved antioxidant activity, and reduced inflammation. More studies are needed in different pregnancy conditions along with the measurement of different biomarkers.