Background: Several evidences suggest that Cytomegalovirus (CMV) may play anetiological role insome case ofschizophrenia and bipolar disorder.Studies have reportedthat some individuals experiencing initial episodes of major mental disorders haveincreased levels of immunoglobulin G(IgG) toCMV.Objective:To determine the magnitude of CMV infection in individualswithschizophrenia,bipolar disorder and healthy controlsby using serologic diagnostic methods.Materials and Methods: A case control studyconducted from March to May of 2009. Atotal of 844 serum samples were analysed for the presence and level ofIgG to CMVusingenzyme linked immunosorbent assay (ELISA).Serawere collected from 216 individualswithschizophrenia, 199with bipolar disorderand 429closerelatives andotherhealthycontrols,recruited from Butajira district.Seropositivity summarized using percentage and antibodylevel was summarized usingmean.Logistic regression was used for cross tabulated dataand linear regression for comparing antibody level among groups. All test of significancewas two tailed and,p < 0.05 is considered significant.Results:99.3% of testedserawere positive for IgG toCMV. However, serum levels of IgGto CMV in individuals with schizophrenia[β = 0.21; 95% CI (0.03, 0.38)]and bipolardisorder [β = 0.20; 95% CI (0.02, 0.37)]were higher compared to healthy controls.Younger individuals with schizophrenia (