Background: Immunopathology is responsible for clinical sequelae of chronic HCV infection, FoxP3+CD25highCD4+ regulatory T cells (Tregs) are the master regulators of several immune functions and monitoring their dynamics during HCV infection and after viral clearance is of great importance. Objective: to investigate alterations in FoxP3+CD25highCD4+Treg cells frequency and their FoxP3 expression level in chronic HCV infected Egyptian patients undergoing interferon-free direct acting antiviral (DAA) therapy in comparison to healthy controls. Methodology: Twenty chronic HCV patients undergoing sofosbuvir/daclatasvir combination therapy were included, circulating FoxP3+CD25highCD4+ Treg cells frequency and their FoxP3 expression were assessed by flow cytometry before and at 2 time points after completing the treatment course, correlated with clinical and radiological data at enrollment and compared to those of 20 healthy anti-HCV negative blood donors. Results: Circulating FoxP3+CD25highCD4+ Treg cells frequency and their FoxP3 expression were significantly elevated in chronic HCV patients before treatment with no correlation to virus load, ALT level or fibrosis grade. Treg parameters falls significantly after sofosbuvir/daclatasvir therapy. Treg frequency remained significantly higher than controls 6 months after treatment. Conclusion: DAA therapy was effective at reducing Treg cells frequency and FoxP3 expression but the persistent higher level than normal after 6 months of viral eradication should be further investigated to find out when they will normalize and their influence on the future course of the disease.