Background: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder of heterogeneous nature. Secreted frizzled-related protein (SFRP) 5 is an anti-inflammatory adipokine implicated in metabolic homeostasis. We aimed to confirm the correlation between SFRP5, metabolic inflammation and PCOS, investigate the predictive value of SFRP5 for PCOS and the involvement of SFRP5 in metformin treated PCOS.Methods: This retrospective case-control study included PCOS and control women (67 vs. 33) for detecting serum SFRP5 and its correlation with metabolic inflammation. Predictive value of SFRP5 for PCOS was evaluated by logistic regression and receiver operating characteristic (ROC) analyses. The effects of metformin on SFRP5 and pro-inflammatory cytokines and ovulation of PCOS with metabolic abnormality (37 vs. 36) were analysed.Results: Plasma SFRP5 levels were decreased in PCOS (odds ratio: 0.78, 95% confidence interval (CI):0.703–0.866, PConclusion: Decreased SFRP5 was associated with metabolic inflammation in PCOS and has a potential role for the supplement of AMH in predicting PCOS. The reverse of serum SFRP5 by metformin indicated that SFRP5 participated in the improvment of follicular development by metformin. Further prospective investigations are needed to confirm these preliminary data.