Polycystic ovary syndrome (PCOS) is associated with alterations in gut microbiota. The cytokine interleukin-22 (IL-22) is produced by immune cells and closely linked to gut immunity, which is tightly controlled by its binding protein (IL-22BP). In this study, we aimed to assess whether IL-22/IL-22BP axis is altered in PCOS at baseline and in response to short-term oral contraceptive (OC) therapy.We have evaluated circulating concentrations of IL-22 and IL-22BP in serum samples of 63 PCOS patients and 39 age- and BMI-matched healthy controls. Blood samples were taken in the early follicular phase of a cycle and stored at -80 °C. Serum IL-22 and IL-22BP levels were measured by ELISA at baseline in both women with PCOS and controls, and after 3 months of OC use in PCOS group. IL-22/IL-22BP ratio was calculated in order to have a better reflection of IL-22 biological activity.At baseline, serum IL-22, IL-22BP concentrations and IL22/IL-22BP ratio were similar between women with PCOS and healthy controls. Three months of OC use along with general lifestyle advice resulted in a significant increase in IL-22/IL-22BP ratio in the PCOS group (62.4 [IQR:14.7-172.7] at baseline vs 73.8 [IQR:15.1-264.3] after OC use respectively p = 0.011).Results of this study show that women with PCOS have similar circulating concentrations of IL-22 and IL-22BP with healthy women and that short term oral contraception is associated with an increase in IL-22/IL-22BP ratio suggesting higher biological activity of the IL-22 system with OC use in PCOS.