Background: Congenital cytomegalovirus infection is currently the leading cause of congenital infection in 0.2-2.2% of live births worldwide leading to variable serious sequalae. The aim of the study was to determine if low birth weight is an indicator of CMV congenital infection evidenced by detecting CMV-DNA in umbilical cord blood at the time of delivery. Methodology: CMV-IgG and IgM antibodies and CMV-DNAemia were assessed in umbilical cord blood of two hundreds newborns, one hundred of whom had birth weight ≤ 2700 gram and/or head circumference ≤ 32 cm. Results: CMV-IgM was not detected, while CMV-IgG was positive in 80-90% of the two hundreds tested newborns. CMV-DNA was detected in four out of the 200 newborns. One of them was over the adopted weight limit (> 2700 gram). Conclusions: CMV-IgM and IgG antibodies assessment was not a potential discriminative test to identify congenitally infected newborns. In addition, low birth weight and small head circumference at birth failed to predict congenital CMV infection. CMV-DNA detection in umbilical cord blood at the time of delivery using real-time PCR of all newborns is recommended as decisive, rapid and non-invasive test.