Neudesin is a neuropeptide hormone involves in female reproduction system via promoting effects of progesterone. Polycystic ovary syndrome (PCOS) is a metabolic and reproductive disorder associated with hypothalamic-pituitary-ovarian axis abnormalities and impaired negative feedback mechanism of progesterone upon gonadotropin-releasing hormone secretion. Our aims were to discover whether neudesin levels were altered in PCOS women comparing to controls and to determine the link of neudesin with hormonal-metabolic parameters in PCOS women. The current research was designed as a case-control study. Sixty-eight subjects with PCOS and 67 age- and body mass index (BMI)-matched subjects as controls were enrolled into the study. Circulating neudesin levels were measured by ELISA. Neudesin levels were significantly lower in PCOS subjects compared to controls (4.07 ± 1.22 vs. 6.02 ± 2.07 ng/ml, < .001). Neudesin exhibited an inversely independent link with luteinizing hormone, free-androgen index, and BMI whereas it showed a positively independent link with progesterone in women with PCOS. Logistic regression analysis revealed that decreased neudesin levels were parallel with increased risk of having PCOS. Decreased neudesin levels were associated with hormonal disturbances in PCOS women, suggesting that neudesin may play a role in pathophysiology of PCOS.