PurposeTo compare the performance of Neutrophil-to-Lymphocyte Ratio (NLR) with that of Platelet-to-Lymphocyte Ratio (PLR) in diagnosing neonatal sepsis (NS).MethodsPubMed and Embase were searched for relevant studies from the inception of the databases to May, 2022. The pooled sensitivity (SEN), specificity (SPE), and area under the receiver operator characteristic curve (AUC) were measured.ResultsThirteen studies involving 2610 participants were included. The SEN, SPE, and AUC of NLR were 0.76 (95%CI: 0.61–0.87), 0.82 (95%CI: 0.68–0.91), and 0.86 (95%CI: 0.83–0.89), respectively, and those of PLR were 0.82 (95%CI: 0.63–0.92), 0.80 (95%CI: 0.24–0.98), and 0.87 (95%CI: 0.83–0.89), respectively. Significant heterogeneity was observed among the studies. Subgroup analysis and meta-regression showed that types of sepsis (p= 0.01 for SEN), gold standard (p= 0.03 for SPE), and pre-set threshold (p<0.05 for SPE) might be the sources of heterogeneity for NLR, whereas the pre-set threshold (p<0.05 for SPE) might be the source of heterogeneity for PLR.ConclusionsNLR and PLR would be of great accuracy for the diagnosis of NS, and the two indicators have similar diagnostic performance. However, the overall risk of bias was high, and significant heterogeneity was identified among the included studies. The results of this study should be interpreted prudently, and the normal or cut-off values and the type of sepsis should be considered. More prospective studies are needed to further support the clinical application of these findings.