Background: Female fertility declined in Karnataka. Oxidative stress leads to anovulation, dysfunctional oocytes, fertilization failure, implantation failure, or miscarriage. Vitamin E (α-tocopherol) has the ability of fertilized egg to implant into uterine wall properly. Aims and Objective: The aims and objectives of the study were to establish the serum concentration of α-tocopherol and lipid peroxide (LPO) level in infertile females of northern Karnataka compared to age-matched control. Materials and Methods: Infertile females 20-35 years of age were selected prospectively, and age-matched fertile females were included in the study and divided into two groups: 45 normal fertile females (Group I) and equal number of infertile females (Group II). Body mass index (BMI), blood glucose level, and hemoglobin (Hb) levels were estimated with standard methods. α-tocopherol concentration was determined by non-antibody coated microplate method by using enzyme-linked immunosorbent assay reader. LPO level was assessed by malondialdehyde quantification using spectrophotometry. Results: Infertile females showed any statistical difference in BMI and random blood glucose, but Hb levels reduced significantly as compared to fertile females. The mean duration of infertility was 5.69 years. In infertile females, serum α-tocopherol was decreased significantly from 16.88 to 8.87 μg/L which is 45.78% and serum LPO level was increased from 1.25 to 2.13 μmol/L, which is 70.40% as compared to fertile females. Conclusion: Infertile females of northern Karnataka showed lower α-tocopherol levels and greater potential for oxidative stress as compared to fertile females. These findings demonstrate imbalance in ROS production and antioxidant.