Background: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine co-morbidity of obesity. Ghrelin is a peptide which regulates food intake and body weight. The aim of this study was to measure ghrelin levels in obesity and PCOS and to evaluate the impact of weight loss on plasma ghrelin level, metabolic, and phenotypic features of PCOS. This prospective comparative study enrolled obese women without PCOS (N = 60) and obese PCOS women (n = 50) and 85 control groups. Body compositions including fat mass (FM) and fat-free mass (FFM) were measured by dual-energy X-ray absorptiometry (DEXA). Plasma ghrelin concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Results: Our results revealed that plasma ghrelin levels were lower in PCOS patients compared to obese (9.49 ±5.59 ng/ml) and controls (48.21 ± 21.09 ng/ml). Moreover, it was negatively correlated to anthropometric measures, glycemic, lipid profile, and the phenotype characteristics of PCOS. Interestingly, after 12 weeks of following the Mediterranean diet (MD)-based weight loss program, ghrelin levels were increased in both obese groups. Conclusion: Successful weight loss leads to increase ghrelin levels in both obese and PCOS groups. Keywords: Ghrelin, PCOS, Weight loss, Mediterranean diet, Obesity