Diarrhea remains a major cause of death in children. Current diagnostic methods largely rely on stool culture and suffer from low sensitivity and inadequate specificity, often leading to inappropriate treatment. The objective of the present study was to use RNA sequencing (RNAseq) analysis to determine blood transcriptional profiles specific for several common pathogenic bacteria and viruses that cause diarrhea in children. We collected whole blood samples from children in Mexico having diarrhea associated with a single pathogen and without systemic complications. Our RNAseq data suggested that the blood signatures can differentiate children with diarrhea from healthy children either with or without bacterial colonization. Moreover, we detected different expression profiles from bacterial and viral infection, demonstrating for the first time the use of RNAseq to identify the etiology of infectious diarrhea. Overall design: 255 whole blood samples from 246 children including children with diarrhea caused by rotavirus (n=60 total; 5 repeated; 55 unique), E.coli (n=55), Salmonella (n=36), Shigella (n=37), adenovirus (n=8), norovirus (n=7), and control children (n=52 total; 4 repeated; 48 unique).