Purpose Secreted frizzled-related protein 4 (SFRP4) is an adipokine involving in apoptotic process during ovulation and energy metabolism. Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder associated with insulin resistance and impaired oocyte maturation as well as apoptotic dysfunctions through oocyte development. Our aim was to determine whether there was an alteration in levels of SFRP4 and if there was an association between metabolic or hormonal parameters and SFRP4 in women with PCOS. Methods We enrolled 80 subjects with PCOS and 80 age- and body mass index (BMI)-matched subjects with normal menstrual cycle into current case-control study. Metabolic and hormonal parameters of enrolled subjects were determined. Circulating SFRP4 levels were measured with ELISA method. Results We found that circulating SFRP4 levels were elevated in women with PCOS with respect to controls (5.87 +/- 1.91 vs. 3.72 +/- 1.29 ng/ml, P < 0.001). We also found a positive association between SFRP4 and insulin resistance, androgens, ovarian follicular number or ovarian volume in women with PCOS. Binary logistic regression analysis revealed that subjects with the highest tertile of SFPR4 levels displayed increased possibility of having PCOS risk compared to those subjects with the lowest tertile of SFRP4 levels. Conclusions Increased SFRP4 levels were not only associated with higher possibility of having PCOS but also related to insulin resistance, hyperandrogenism, ovarian follicular number and ovarian volume, suggesting that SFPR4 could be a player in different pathophysiologic pathways of PCOS.