Background: In light of the pending update of the French guidelines for the management of neonatal infections, knowing the current epidemiology of early-onset neonatal infection (EONI) is essential. Objectives: The aim of this study was to assess the current epidemiology of a French administrative district population of proven EONI, including umbilical cord blood procalcitonin levels. Methods: We conducted a retrospective population-based study in the Nantes metropolitan area. We included all infants treated for proven EONI in the maternity, neonatology, and intensive care wards between 1 January 2006 and 31 December 2015 in the Nantes University Hospital. Results: Among the 140,502 children born during the study period, 61 cases of EONI were documented. The overall incidence of confirmed EONI was 0.43/1000 live births, with 0.23/1000 GBS (group B streptococcus) infections and 0.08/1000 Escherichia coli infections. The majority of infected newborns were full-term or late-preterm infants (67% were 34 weeks of gestation), 88% had symptoms of EONI in the first 24 h of life, most of which were respiratory. The mortality rate was 8% (in premature infants). Available in 51% of the population, the cord blood PCT value could contribute to an earlier diagnostic screening in 10% of cases but with a very low sensitivity. Conclusions: The incidence of confirmed EONI is low in this French district. The diagnostic value of PCT umbilical blood cord should be assessed based on further studies before confirming its value. We suggest that a national registry of these rare but serious cases of EONI could contribute to monitoring the epidemiological progression as well as to optimizing our diagnostic and therapeutic strategies