In immunocompetent patients with liver inflammation, the detection of IgG and IgM antibodies against the hepatitis E virus (HEV) is important for the diagnosis. Recently, fully automated chemiluminescence immunoassays (CLIAs, LIAISON® Murex anti-HEV IgG/anti-HEV IgM test, DiaSorin) have become available for this purpose. The diagnostic suitability of these CLIAs was determined by comparison with a combination of plate-based enzyme immunoassays ( recomWell HEV IgG/IgM ELISA, Mikrogen) and immunoblots ( recomLine HEV IgG/IgM, Mikrogen), which served as a reference for the characterization of sera. Samples with a deviating result were retested with an alternative test (WANTAI HEV IgG/IgM ELISAs). The anti-HEV IgG CLIA had a sensitivity and specificity of 100% (100/100; 49/49) each when the recomWell HEV IgG ELISA served as a reference. The anti-HEV IgM CLIA had a sensitivity of 67.9% (36/53) and a specificity of 100% (49/49). When IgM immunoblot results were considered, sensitivity and specificity were 88.9% (24/27) and 53.8% (14/26), respectively. The WANTAI test confirmed 52.9% (9/17) of negative CLIA IgMs that differed from the recomWell HEV IgM result. The CLIA revealed an isolated and thus probably non-specific HEV IgM in one of 17 patients with acute Epstein-Barr virus infection. The automated CLIAs are well suited for HEV diagnostics.