Background: Knee osteoarthritis (KOA) represents a chronic, multifaceted condition characterized by degenerative afflictions predominantly targeting the knee joint, a commonly implicated site in osteoarthritic pathologies. Adropin, a peptide hormone encoded by the energy homeostasis associated (ENHO) gene, that exhibits extensive expression across multiple tissues, notably in the liver, brain, heart, kidneys, pancreas, coronary arteries, and umbilical veins. Furthermore, adropin is discernible within a broad spectrum of bodily fluids, including plasma, serum, and exocrine secretions like colostrum and milk, indicating its pervasive role and systemic relevance in physiological processes. Objective: Measurement of Serum Adropin level in knee osteoarthritis patients and its relationship with clinical manifestations, different radiological grading and ultrasonographic findings. Methodology This case control study has been conducted on 40 patients with varying grades of knee osteoarthritis were compared to 40 age and sex-matched healthy people as controls. The serum adropin level has been measured in both groups using the enzyme linked immunosorbent assay (ELISA) technique. Results: As regards adropin level, there were statistically significant differences between patient group with a mean of (266.12±65.75) compared with the control group with a mean of (582.63±129.73, p < 0.001). There was a negative correlation between adropin level “pg/ml" and Western Ontario and McMaster Universities (WOMAC) grading with p-value (< 0.05). There was negative correlation between adropin level “pg. /ml “and Kellgren Lawrence (KL) grading (r = - 0.909, p < 0.05). Conclusion: Serum adropin concentrations were markedly reduced in patients with KOA relative to control subjects, demonstrating a specificity of 87.5% and a sensitivity of 90%. There exists a negative association between serum adropin levels and several clinical indicators: Kellgren Lawrence (KL) grading scale, cartilage thickness, the Western Ontario and McMaster Universities (WOMAC), and visual analogue scale (VAS). Consequently, serum adropin measurements may serve as both a sensitive and specific diagnostic biomarker for knee osteoarthritis