Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease with significant mortality. Two testing methods are currently used for MERS-CoV diagnostics: nucleic acid detection (the gold standard) and serological analysis. In this study, we evaluated the detection of MERS-CoV-IgG in suspected and proven cases of MERS-CoV infection. We enrolled 174 patients: 113 had respiratory symptoms/suspected MERS-CoV infection, 31 had confirmed influenza A or B infection, 23 had a recent confirmed MERS-CoV infection, and 7 had confirmed MERS-CoV infection 1 year before. All underwent MERS-CoV RNA and MERS-CoV-IgG testing. Thirty patients were found to be MERS-CoV RNA positive; however, during serological analysis, only 6 (3.4%) patients were positive for MERS-CoV-IgG, 1 (0.6%) patient was equivocal, and 167 (96%) patients were negative. Among the serological positives, four were recently MERS-CoV RNA positive and two were MERS-CoV RNA negative. No cross-reactivity to influenza A or B was detected. Based on the lack of correlation between nucleic acid and serological analysis, we conclude that MERS-CoV-IgG testing may not be suitable for diagnosing acute infection or estimating its prevalence during an outbreak. In addition, our findings show that MERS-CoV-IgG may not have significant value in determining disease severity or prognosis.