Background: PCO is a metabolic disorder, and its pathogenesis is still unclear, but the changes in the hypothalamic-pituitary-gonadal (HPG) axis are considered one of the main causes in the development of PCO. Kisspeptin is a peptide encoded by the KISS gene that regulates the hypothalamus-pituitary-gonadal (HPG), which may be concerned with the pathogenesis of PCO. Aim: To identify the serum Kisspeptin relation with hormonal and metabolic profiles among normal and PCO women. Methodology: A prospective case-control study was conducted among 64 subjects (32 with PCO and 32 with the control group). The serum Kisspeptin level was measured using enzyme-linked immunosorbent assay (ELISA) and correlated with other hormones such as LH, FSH, DHEA, testosterone, and prolactin. Results: Serum kisspeptin level was significantly higher in the PCO group when compared to the control group. There was a statistically significant positive correlation between kisspeptin and each of HOMA IR, LH, FSH, DHEA, testosterone, and prolactin. Conclusion: The increase in kisspeptin level may play a role in pathogenesis of PCO, and may represent a novel link between metabolic and hormonal disturbance in PCO females since this peptide was correlated with HOMA-IR, LH, FSH, DHEA, testosterone and prolactin.