Background: Two recently discovered circulating proteins, pentraxin 3 (PTX3) and betatrophin, have a strong correlation with a number of illnesses, obesity, and the metabolic syndrome. Objective: This study was made to investigate whether pentraxin-3 (PTX3) and betatrophin levels are sensitive markers associated with PCOS in women with or without diabetes. Materials and methods: We conducted a case-control clinical study. Samples were collected from "infertility center" at Basra hospital for Obstetrics and children in Basra province-Iraq during the period from August 2023 till end of February 2024. Results: Levels of Ts, PRL, HOMAIR, PTX3, betatrophin, and MDA were elevated (p < 0.01), LH and insulin were increased (p<0.05) and (p<0.01), E2 and TAC decreased (p<0.01), while BMI and FSH levels showed non-significant changes (p>0.05) in PCOS women with or without diabetes (both 1ºPCOS and 2ºPCOS), respectively, as compared to the healthy control. Glucose was increased (p<0.01) in PCOS women with diabetes (both 1ºPCOS and 2ºPCOS), and AMH had increased (p<0.05) in PCOS women without diabetes. The area under the curve (AUC) indicate that PTX3 (AUC= 0.95, 0.90, 0.88, 0.85) and betatrophin (AUC= 0.89, 0.87, 0.86, 0.85) could potentially be used as greater predictive biomarkers in PCOS women (both 1ºPCOS and 2ºPCOS) with or without diabetes. Conclusion: Dysregulation of PTX3 and betatrophin may be associated with the metabolic consequences of PCOS. Therefore, we suggest that PTX3 and betatrophin may potentially serve as an independent predictor for the prognosis and development of PCOS in at-risk women, especially those with insulin resistance.