Background: Antibiotics are central to the initial treatment of sepsis in neonatal intensive care units (NICU). But, due to Drug-Related problems (DRP), many neonates do not experience the expected effects of treatment. The objective of this study was to identify the DRPs associated with antibiotics, as well as their associated factors and effects on outcomes, in neonates diagnosed with sepsis within 72 hours of birth. Methods: A prospective observational study involving 223 neonates with sepsis admitted to the NICU was conducted from 1 June to 30 November 2021. A panel of experts designed and validated the data collection form, comprising five sections: neonatal, maternal, delivery, lab finding, and pharmacological treatment information. Logistic regression was used to establish the DRPs determinants. A p-value< 0.05 was deemed statistically significant. The Kaplan–Meier method was used to compare neonates’ survival rates with and without DRPs. Results: Ampicillin (70.2%) and Gentamicin (50,5%) were the most frequently used antibiotics. At a rate of 39.91%, 129 DRPs of antibiotics were identified in 89 neonates [95% CI: 32.8–47.01]. Ineffective antibiotics (36.4%) and excessive dosages (24%) were the most common DRPs identified. Two or more antibiotics exposure [AOR=3.8, 95%CI [0.8-12.8], p=0.031] and diarrhea [AOR=1.8, 95%CI [1.2-2.4], p=0.014) were determined of DRPs. Significant outcomes of antibiotic DRPs included persistent infection, septic shock, new infection focus, and mortality within 30 days due to any cause. Conclusion: The effectiveness of drug therapy is impacted by the use of inappropriate antibiotics and dose selection. Two or more antibiotics exposure and diarrhea were associated with an increased risk of DRPs and unfavorable outcomes.