Background: Arginine vasopressin (AVP) affects liver glycogenolysis, insulin, and adrenocorticotropic hormone release supporting its role in metabolic disorders. Copeptin is established as a stable and sensitive biomarker of AVP level. Aims and Objectives: The aim of the study is to investigate the association between serum copeptin level and metabolic syndrome (MetS) parameters in both male and female albino rats. Materials and Methods: Sixteen male and 16 female adult rats were subdivided into control and high-carbohydrate high-fat (HCHF)-fed groups. Body mass index (BMI), systolic, diastolic, and mean arterial blood pressure (MABP) were measured. Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucose, insulin, highly sensitive C-reactive protein (hs-CRP), and copeptin were estimated. Homeostatic model assessment for insulin resistance (HOMA-IR) and atherogenic index (AI) were calculated. Results: There was significant increase in BMI, blood pressures, and levels of TC, TG, LDL-C, AI, glucose, insulin, HOMA-IR, hs-CRP, and copeptin with significant decrease in HDL-C level in male and female HCHF-fed groups compared with their controls. All parameters except HDL-C, blood pressures, and hs-CRP were significantly lower in female HCHF-fed group compared with male HCHF-fed one. There was positive correlation between copeptin level and BMI, insulin, glucose, HOMA-IR, TC, TG, LDL-C, AI, and hs-CRP and negative correlation with HDL-C with insignificant correlation with MABP in both HCHF groups. Conclusion: HCHF-fed male rats are more subjected to develop features of MetS with more elevation in copeptin than female rats. Elevated copeptin was correlated with components of MetS as obesity, hyperglycemia, IR, dyslipidemia, and hs-CRP in both sexes indicating the role of the vasopressinergic system in the pathogenesis of MetS. Further studies to evaluate copeptin as a predictive marker for MetS and therapeutic role of controlling AVP based on gender difference are recommended.