Background: many extrahepatic manifestations including autoimmune, rheumatic disease and metabolic bone impairment have been stated in hepatitis C virus (HCV) infected patients. Direct antiviral agents (DAAs) are major developments in the treatment of HCV infection and were reported to have effect on the musculoskeletal manifestations. Objectives: to evaluate the effect of hepatitis C and direct antiviral agents (DAAs) on musculoskeletal system, bone mineral density (BMD). Methods: the current study involved 60 patients with hepatitis C, 30 patients with no history of anti-viral agent’s treatment (group I) and the other 30 patients achieved response on DAAs within the last year (group II). All patients were subjected to history taking, physical examination, investigations including (calcium, Phosphorus, Parathormone hormone, alkaline phosphatase and vitamin D) and DEXA scan for BMD measurement. Results: In this study, group I showed significantly lower bone mineral density compared to group II . The frequency of musculoskeletal manifestations caused by HCV in group I is higher than group II including: arthralgia (70%), sicca symptoms (50%), fatigue (40%), fibromyalgia (20%), arthritis and cryoglobinemic vasculitis (10%). Conclusion: Musculoskeletal manifestations including decreased BMD are frequent in chronic hepatitis C (CHC) patients and treatment with DAAs proved a beneficial impact.