Neonatal sepsis has non-specific and variable clinical manifestations that can worsen rapidly. Thus clinicians will tend to have a low threshold for giving antibiotics. Early diagnosis of sepsis based on clinical and laboratory manifestations is required to initiate antibiotics without waiting for culture results. The sepsis calculator is a validated tool used and researched in various countries to predict the risk of early-onset sepsis. This systematic review and meta-analysis study used secondary data from articles between 2015 to 2020 from the PubMed database, Google Scholar. There were six lead articles that matched the inclusion and exclusion criteria. By analyzing using the Revman Review Manager 5.4. the results showed that the implementation of the sepsis calculator was associated with reduced antibiotic usage (N=172385; OR=0,22;p<0,00001) heterogeneity I?=99%). From this study, it was found that there was an association between sepsis calculators with antibiotic usage in neonatal with early-onset sepsis.