Abstract Background: Polycystic ovary syndrome (PCOS) is a hormonal disorder common among women of reproductive age and affects over than 10% of these women. The hormonal derangement associated with PCOS is uniformly characterized by excess androgens and abnormal insulin activity. Aim of Study: Estimation of serum levels of spexin (SPX) in women with polycystic ovary syndrome (PCOS) who had non-alcoholic fatty liver disease (NAFLD) and to evaluate its relation to the diagnostic markers of both diseases. Patients and Methods: 102 PCOS women with NAFLD were evaluated clinically and by ultrasound for estimation of ovarian size and determination of liver steatosis grade. Blood samples were obtained for estimation of serum SPX, testo-sterone, dehydroepiandrosterone sulfate (DHEA-S), lipid profile, aspartate transaminase (AST) and alanine transaminase (ALT) and the AST/ALT ratio (AAR) was calculated. Results: All women showed significantly high serum testosterone, DHEA-S, blood lipid profile with high homeos-tasis model assessment of IR (HOMA-IR) score, while showed significantly lower serum SPX levels than control women. Sixty-nine women had ovarian size of >10cm3, and 36 and 5 patients had steatosis of grade 1 and 2, respectively. Serum SPX levels showed negative significant correlations with liver steatosis grade, HOMA-IR, ovarian size, BMI, serum testo-sterone, TG, TC and AAR; while showed positive significant correlation with serum HDL-c. Liver steatosis grade showed positive significant correlation with serum testosterone, ovarian size, BMI, AAR, HOMA-IR score, serum levels of DHEA-S, lipids. Regression analysis defined low SPX, high testo-sterone, LDL-c and DHEA-S levels are for high liver steatosis grade in PCOS women. Conclusion: Serum SPX concentrations were significantly decreased in patients had PCOS and NAFLD and was corre-lated with their associated disturbances. Spexin could be considered as the cornerstone for regulation of the relation between PCOS and NAFLD.