Introduction: According to WHO, the primary infertility in India is about 3.9% (age-standardized to 25-49 year) and 16.8% (age-standardized to 15-49 year), using the "age but no birth" definition. Several factors which affect fertility include low sperm production in men, poor egg quality and blocked fallopian tubes in women and also hormonal imbalances. Leptin plays a critical role in women's reproduction and neuroendocrine health. It is used for treating exercise-induced bone loss, eating disorders and infertility. Aim: To evaluate the serum leptin levels in Indians and to ascertain the relationship between serum leptin levels, Unexplained Infertility (UI) and related variables [ height, weight, Waist Hip Ratio (WHR), Body Mass Index (BMI)] between obese infertile, non-obese infertile and healthy subjects. Materials and Methods: The present case-control study was conducted at the Department of Obstetrics and Gynaecology, King George's Medical University (KGMU), Lucknow, India and funded by Department of Science and Technology, New Delhi, India. The study included 229 female participants in the age group of 18-40 years (120 cases and 109 controls) who were randomly selected. The blood samples were collected from the Infertility Clinic, Queen Mary's Hospital, KGMU, Lucknow, India. All the participants underwent complete physical examination. Initially, the participants were categorized into fertile and infertile groups, they were further divided on the basis of BMI, normal (BMI-18.5-24.5) and overweight or obese (BMI >= 25). Leptin level was measured by Active Human Leptin ELISA kit and BMI of all subjects was calculated in kg/m(2) (weight in kg and height in m). Results: A highly positive linear correlation (R=0.754, p<0.001) was found between BMI and serum leptin in unexplained infertile women, which indicates a strong relationship between BMI and serum leptin. The variation in serum leptin is explained by the independent variable, BMI. There was a partial positive linear correlation between BMI and serum leptin in the control group. Statistically there was no significant correlation (R=0.109, p=0.258) between BMI and serum leptin in the control group. Conclusion: The present study clearly demonstrates that level of leptin is higher in unexplained infertile than in the fertile group, and also shows that a strong relationship exists between BMI and serum leptin in the obese group. Serum leptin level was significantly higher in obese than non-obese subjects. Thus, leptin is an important factor for normal reproductive function. Obesity, the main cause of infertility may be controlled by regulating the leptin concentration.