Background: Apart from genetic factors, epigenetic mechanisms like DNA methylation are now being established for their association with human diseases. Despite advance in medical research, sepsis still remains the major cause of neonatal mortality. In this study, the role of DNA methylation in neonatal sepsis was studied in an epigenome wide scale and the candidate genes were functionally annotated. Methods: The methylation status was analyzed in babies with and without sepsis in epigenome wide scale using Illumina Infinium Human Methylation 450K methylation microarray. The microarray data was functionally annotated and interpreted for their biological significance using the bioinformatics softwares and databases like DAVID v6.7, GeneMania, KEGG, etc. Results: Functional annotation of methylation microarray data revealed that the protocadherin beta group of genes was hypermethylated in babies with neonatal sepsis. Protocadherin beta genes was found to be associated with calcium dependent cell to cell adhesion which is important in signaling pathways like leukocyte migration during sepsis. Conclusion: DNA methylation might play critical roles in neonatal sepsis which was obvious from differential methylation of candidate genes like protocadherins, modifying the associated biological pathways.