Active maternal cytomegalovirus (CMV) infection is the bedrock of congenital CMV with its debilitating sequelae. Information on socio-biologic predictors of active maternal infection in southwest Nigeria is lacking. However, modifying locality-specific risk factors could reduce the burden of CMV. The aim of the study is to identify the socio-biologic determinants for active maternal CMV infection in a Nigerian setting. Using a cross-sectional design, ELISA kits were employed to quantify the anti-CMV IgG and IgM antibodies in the sera of consecutive antenatal attendees at the Ekiti State University Teaching Hospital (EKSUTH), Nigeria. Among the respondents, 23 (12.4%) were seropositive for both anti-CMV IgG and IgM antibodies. The regression analysis showed that the likelihood of being seropositive for both anti-CMV IgG and IgM antibodies was predicted by having a child less than 5 years old (adjusted OR: 5.53; 95% CI: 1.08 – 28.30; p = 0.04), while those who were skilled workers were least likely to be seropositive for both antibodies (adjusted OR: 0.06; 95% CI: 0.01 – 0.95; p = 0.04). Also, infection with cytomegalovirus was associated with pre-eclampsia (adjusted OR: 0.03; 95% CI: 0.002 – 0.41; p = 0.01). High prevalence of active maternal CMV infection was noted from the study, and this was associated with pre-eclampsia and caring for children under-5. Educating pregnant non-immune women about CMV and its prevention, coupled with the improvement in socio-economic status of the populace can reduce the burden in low-resource settings.