Background: Infertility is well-known global health problem that has significant impacts on an individual, families and communities. Many modifiable lifestyle risk factors increase the risk of women to several reproductive disorders. Aim: This study established the relationship between obesity and Hypothalamic-Pituitary-Ovarian (HPO) axis hormones in infertile women in the Niger Delta Region, Nigeria. Methodology: Six hundred and twenty-six (626) women aged 18 -40 years comprising of 513 obese infertile women and 113 non obese women who served as control were recruited for the study. Anthropometric measurements were taken and Body Mass Index was calculated. A non-fasting venous blood sample was collected from the women and analyzed for serum Estrogen, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), Progesterone, Inhibin B, and Prolactin using Enzyme linked immunosorbent assay method. Results: In the present study, the Body Mass Index of women with primary (1˚) infertility is significantly (p < 0.05) higher than secondary (2˚) infertility women. Whereas, women with 2˚ infertility were older and have a higher height than women with 1˚ infertility. The result revealed that serum estrogen, luteinizing hormone, follicle stimulating hormone and prolactin levels were significantly (p < 0.05) higher in the obese infertile women, while inhibin B and progesterone levels were significantly (p < 0.05) reduced in the obese infertile women compared to the control subjects. However, women with 1˚ infertility have a significantly higher LH and FSH levels than the 2˚ infertility women. Furthermore, the study revealed that hyperestrogenism is the most prevalent gonadal disorder in women with primary infertility and secondary infertility. The BMI of infertile women suffer-How to cite this paper: Nelson, O.E. and Chukwuma, E.F.