Background: Diagnosis of prolonged febrile illness of unknown origin (FUO) is challenging even with the advances in the diagnostic techniques. As common as the infection with cytomegalovirus (CMV) is, most health care providers would not suspect CMV infection as a cause of FUO unless mononucleosis syndrome is evident. The aim of this study is to investigate the rate of CMV infection among patients with FUO and shed light on IgG avidity as a diagnostic tool. Patients and methods: Two hundred and twenty three (223) immune competent patients with FUO were included in our study. They were subjected to all routine laboratory investigations, fever agglutinins, tuberculin and abdominal ultrasound along with IgG and IgM for CMV and IgG avidity test. Results: This study shows that the 92.8% of the overall studied population were positive for CMV IgG. However, only 74(33.2%) of the studied population was found positive for IgM. Only one patient had positive IgM with negative IgG. IgG avidity was high in almost all of them. Only 3 patients showed low IgG avidity denoting that they have primary infection. Conclusion: CMV infection was found to be the cause of 33.2% of prolonged febrile illness experienced by immuncompetent adults. Only 1.8% of patients had primary CMV infection and the majority of them had detectable IgG level and were diagnosed with primary infection depending mainly on IgG avidity test.