Background <p>Early-onset neonatal infections (EONIs) are those infections diagnosed in newborns aged lesser than 72&#xa0;h and constitute a public health problem in both industrialized and developing countries. The objective of this study was to determine the incidence and identify the risk factors of EONIs in the health facilities of the Katwa Health Zone.</p> Methods <p>This was longitudinal and descriptive study of the incidence of hospital-based EONIs from January 1, 2020 to December 31, 2022, in four health facilities of the Katwa Health Zone: Matanda, Wahamahika, and Sainte Famille Hospitals, and the Katwa General Referral Hospital. All newborns aged lesser than 72&#xa0;h, found in the maternity ward and/or the neonatology department and whose sheets contained the study parameters, were included. EONIs were suspected by clinical symptoms (e.g., fever) and confirmed by laboratory exams (WBC, culture). The following variables were analyzed: Newborn risk factors (gestational age, sex, weight, history) and mother (mother’s age, origin, marital status, occupation). The statistical analysis was performed by Epi-INFO version 7.</p> Results <p>The incidence of intra-hospital EONIs was 3.54%. The risk factors related to the newborn are: gestational age inferior to 37&#xa0;weeks (OR = 2.84; EFs = 64.79%), weight inferior to 2000&#xa0;g (OR = 4.99; EFs = 79.96%), history of a premature rupture of membranes (OR: 9.53; EFs = 89.91%), maternal fever (OR = 6, 82; Fes = 85.34%), lower than 4 prenatal consultations (OR = 2.28, EF = 56.14%), APGAR score bellow to 8 (OR = 3.14; EF = 68.13%) and meconial amniotic fluid (OR = 2.74; EFs = 63.50%). Mother’s age under 18 was associated with 55.56% (OR = 2.25; EFs = 55.56).</p> Conclusion <p>Refocused antenatal consultations would be of great importance to limit the risks of maternal–fetal infection, a public health challenge.</p>