Introduction and aim: Osteoarthritis (OA) is the commonest degenerative and painful articular disease. It is a significant cause of disability. Early diagnosis is crucial and searching for biomarkers is continuing. The current work aimed to assessment the plasma leptin and adiponectin concentrations in patients with primary knee osteoarthritis (OA), and to explore the relationship of leptin and adiponectin with OA severity Methodology: Forty patients with primary knee osteoarthritis from both sexes who fulfilled ACR criteria for diagnosis of knee OA were enrolled. Other healthy subjects were included as a control group.  Patients were sassed by history taking, clinical examination, radiological and laboratory investigations. WOMAC questionnaire was used to evaluate a patient’s functions. Results: Both study and control groups were comparable as regards to patient demographics, except their weight, height and body mass index (BMI). Obesity, hypertension, tenderness, pain grade, limitation of joint movements and WOMAC score, Kellgren Lawrence radiological criteria, leptin and adiponectin were increased in study when compared to control group.  There was significant, positive, moderate correlation between leptin and BMI (r=0.557, p < 0.001). Higher leptin was associated with obesity and diabetes mellitus. Leptin serum levels revealed proportional, moderate, significant correlation with each of pain, stiffness and K-L criteria, while this correlation was powerful with physical function and total WOMAC score. Conclusion: Leptin and adiponectin were increased in patients with osteoarthritis. Leptin alone is significantly associated with disease severity indices.