Background: Like other viruses, hepatitis C virus (HCV) needs constituents of host cells to proliferate and iron is considered as one of the most important constituents. So, chronic HCV often appears to be associated with disturbances in iron homeostasis. Objective: The aim of this study was to evaluate the iron metabolism dynamic changes in response to direct antiviral agents (DAAs) among Egyptian chronic HCV patients. Patients and Methods: This prospective cohort study was conducted on 180 subjects, 150 of them had chronic HCV whom received different DAAs regimens at one of the specialized HCV treatment facilities (Group A), as well as another 30 healthy volunteers (Group B), in the period from January 2017 to September 2018. The study was approved by the medical ethics committee of Al-Azhar University Hospitals and a written informed consent was obtained from all patients. Result: Before treatment, serum iron, ferritin, transferrin saturation and triglycerides were significantly higher among HCV patients when compared to controls (p<0.001), while serum TIBC, transferrin, hepcidin, hepcidin/Ferritin ration, cholesterol were significantly lower in HCV patients in comparison with controls (p<0.001). Following treatment with DAAs, serum iron, ferritin, transferrin saturation and triglycerides were significantly decreased. On the other hand, serum TIBC, transferrin, hepcidin, hepcidin/Ferritin ration and serum cholesterol were significantly increased. The improvement of HbA1c was associated with an improvement in iron overload parameters. Conclusion: Rapid decrease in serum ferritin during IFN/RBV free treatment may reflect a quick regression of inflammation after inhibition of viral replication. The improvement in the iron parameters associated with improvement in triglyceride and glucose metabolism may also suggest an improvement of metabolic functions of the liver following HCV eradication.