Background <p>To compare the clinical characteristics and outcomes of early-onset neonatal bacterial meningitis (NBM) in preterm and full-term infants.</p> Methods <p>This retrospective study analyzed neonates diagnosed with NBM within 7 days (based on symptom onset) of birth at authors’ hospital (2005–2024). Participants were stratified into preterm (&lt; 37 weeks) and full-term (37–42 weeks) groups. Data on perinatal factors, clinical presentation, laboratory results, and outcomes were compared.</p> Results <p>A total of 74 infants (33 females, 41 males) were included, with 17 in the preterm group and 57 in the full-term group. Preterm infants had higher rates of premature rupture of membranes (PROM; 52.94% vs. 8.77%, <i>p</i> &lt; 0.001), apnea (35.29% vs. 1.75%, <i>p</i> &lt; 0.001), and respiratory support need (58.82% vs. 12.28%, <i>p</i> &lt; 0.001), but lower fever incidence (41.18% vs. 80.70%, <i>p</i> = 0.004). <i>Escherichia coli</i> (37.10% of blood culture-positive cases) and <i>Group B Streptococcus</i> (<i>GBS</i>) (30.65% of blood culture-positive cases) were predominant pathogens. Overall cure and mortality rates (60.81% and 9%, respectively) did not differ significantly between groups.</p> Conclusion <p>Preterm infants with early-onset NBM had higher rates of apnea, respiratory support, and PROM, but lower incidence of fever compared to full-term infants. These differences highlight the need for early recognition and tailored management in preterm cases.</p> Clinical trial number <p>Not applicable.</p>