Few studies on the immunoglobulin E (IgE) immune response in chronic hepatitis C have been reported. In this study, we tested the antigenicity of commercial recombinant hepatitis C virus (HCV) core and nonstructural protein NS3, NS4, and NS5 antigens and the IgE immune response to these antigens in chronic hepatitis C patients before and after antiviral treatment with pegylated interferon (IFN)-α plus ribavirin for 12 weeks. The effects of antiviral treatment were investigated in 20 out of 35 participants. We developed amplified immunoassays using these antigens and IgG-depleted patient sera. Seropositivity for IgE antibodies was determined, and serum IgE and cytokine levels were measured. Anti-core, anti-NS3, and anti-NS4 IgE antibodies were observed in most patients, whereas anti-NS5 antibodies were less prevalent. Antiviral treatment decreased the production of anti-core, anti-NS3, and anti-NS4 IgE antibodies, but not anti-NS5 IgE antibodies. A significant decrease in the anti-NS3 and anti-NS4 IgE antibody levels was observed in patients who presented with an early sustained virological response, but no effects on anti-core and anti-NS5 IgE antibodies was observed. The serum levels of IFN-γ, interleukin (IL)-2, IL-6, tumor necrosis factor-α, and IL-10, but not IL-4, were similar between patients before and after antiviral therapy. Thus, the immune response of IgE antibodies to HCV antigens was comparable to that of anti-HCV IgG antibodies. The usefulness of anti-NS3 IgE antibodies in diagnosing occult hepatitis C and monitoring antiviral treatment with directly acting antiviral medication must be investigated in future studies.