Background: Early-onset sepsis (EOS) is a leading cause of morbidity and mortality among neonates. Diagnosis of EOS can be difficult as clinical signs are subtle. The use of the Neonatal EOS Calculator (NEOSC) may help screen high-risk neonates for EOS and may result in a significant reduction in unnecessary antibiotic use. Objective: To determine the diagnostic accuracy of the NEOSC in screening for EOS in neonates more than 35 weeks age of gestation. Methodology: This was a retrospective, case-control study where 245 septic (cases) and 245 non-septic (controls) neonatal and maternal medical records were reviewed. The EOS risk classification from the NEOSC was compared with the actual clinical outcome. An online statistical software (medcalc.org) was used to compute for the sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and accuracy of the NEOSC. Results: Based on the NEOSC, only 64 of 245 clinically septic neonates were truly positive for sepsis while 181 were falsely negative for sepsis. Of the 245 non-septic neonates, 3 were falsely positive for sepsis, while 242 were truly negative for sepsis. With a 95% confidence interval, the computed variables showed a Sn 26.12%, Sp 98.78%, PPV 76.12%, NPV 89.95%, PLR 21.33, and NLR 0.75. The accuracy of the NEOSC is 89.33%. Conclusion: The NEOSC had poor sensitivity and is not recommended in screening for EOS in neonates more than 35 weeks age of gestation. It may be used as an adjunct in EOS diagnosis due to its high specificity and accuracy.