Aim: To evaluate the role of free radical induced oxidative stress in the etiopathogenesis of unexplained infertility by biochemical estimation of oxidants and antioxidants levels. Objectives: • To evaluate the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione reductase before antioxidant supplementation. • To compare the effect of antioxidants (vitamin C 790 mg/day, vitamin E 15 mg/day, zinc 10 mg/day, Se 55 μg/day) given for 6 months on fertility outcome in patients with unexplained infertility by evaluating the levels of MDA, SOD, and glutathione reductase post supplementation. Materials and method: This prospective study is carried out on 100 patients in LLR and associated hospital, Department of Obstetrics and Gynaecology, Kanpur, during the period from January 2014 to October 2015. Specific investigation of lipid peroxidation product MDA, SOD, and glutathione reductase (GR) was done initially at the 1st visit (baseline level) and then after supplementation of antioxidants for 6 months. Patients with other causes of infertility were excluded. Results: Out of 100 patients, 30 were controls with spontaneous conception, and 70 were patients with unexplained infertility. Out of these 70 patients, 36 were given antioxidants from outside. Levels of MDA were significantly higher, and levels of GR and SOD were significantly lower in patients with unexplained infertility when compared with patients with spontaneous conception. There was an improvement in pregnancy outcome by supplementation with antioxidants from outside. Conclusion: An imbalance in the level of oxidants and antioxidants leading to oxidative stress can affect the quality of gametes and can be the cause of unexplained infertility. Antioxidant supplementation from outside can improve fertility outcomes in these patients.