Background: Osteoarthritis (OA) is considered one of the most common musculoskeletal disorders and the leading causes of disability nowadays. IL-6 plays a key role in local and systemic manifestation of OA. Objectives: The aims of this work were to evaluate the level of serum IL-6 and its correlation with the activity, severity, disability, early development of osteoarthritis and early structural bone damage in OA patients using Western Ontario and McMaster Universities Osteoarthritis (WOMAC), Modified Health Assessment Questionnaire disability (M.HAQ) and Kellgren and Lawrence (K-L) scores. Methodology: This case-control study had been conducted on 40 patients with OA attending the Rheumatology and Rehabilitation outpatient clinic, Beni-Suef University Hospital from December 2017 until April 2018. The study included 20 healthy individuals as well. The following parameters were investigated: IL-6 serum level, BMI, ESR, CRP, CBCs, Kidney function tests (blood urea and serum creatinine) and liver function tests (AST and ALT). Radiological assessment was done by plain X-ray to the affected joint. Drug history was taken stressing on steroid therapy. Data were processed and analyzed using computer-based program. Results: The results of the study revealed higher levels of IL-6 in serum of OA patients which was significantly correlated with WOMAC, M.HAQ, K-L scores, ESR and CRP. Conclusion: IL-6 may play a synergistic role in OA pathogenesis and the degree of severity and disability of the disease, so it can be used as a biomarker for disease diagnosis and predictor of disease progression.