<p>Background: Polycystic ovary syndrome (PCOS) is a heterogeneous condition that encompasses several cardiometabolic and endocrinological disorders. Studies have shown that its pathogenesis aligns with several underlying mechanisms associated with recurrent pregnancy loss (RPL). Cellular communication network (CCN)-3 protein is a well-studied adipokine involved in tumorigenesis, organogenesis, inflammation, fibrosis, and glucose metabolism. The purpose of the current study was to determine the association of CCN3 levels with a number of parameters involved in PCOS pathogenesis.<br /> Methods: This is a case-control study including 120 PCOS patients (60 cases with RPL; PCOS-RPL and 60 cases with infertility; PCOS-Inf and 60 healthy controls). Circulating levels of homocysteine and high-sensitivity C-reactive protein (hs-CRP), homocysteine, and CCN3 were measured using ELISA kits.<br /> Results: Circulating levels of CCN3 were significantly elevated in PCOS-RPL and PCOS-Inf subgroups when compared to the control group (7.61&plusmn;3.03 and 6.85&plusmn;2.54 vs. 3.12&plusmn;0.82, p&lt;0.001). Serum CCN3 positively correlated with fasting insulin and homeostatic model assessment of insulin resistance (HOMA-IR) in the control group (p&lt;0.05) and PCOS group (p&lt;0.001). Moreover, CCN3 was significantly associated with PCOS (OR 4.808, 95%CI [2.744-8.423], p&lt;0.001).<br /> Conclusion: According the results of this study CCN3 may be involved in the pathogenesis of PCOS. However, future studies are needed to evaluate the possibility of utilizing CCN3 in the diagnosis and treatment of the disease.</p>