Porcine epidemic diarrhea (PED) was triggered by pathogenic coronavirus causing watery diarrhea and high mortality in piglets. This post-viral syndrome results in severe economic losses in the pig industry. However, limited information on the porcine epidemic diarrhea virus-infected pigs is available. Thus, the objective of this study was to identify transcriptomes with RNA sequencing (RNA-seq) in peripheral blood mononucleated cell (PBMC) of piglets, Large White x Landrace crossbreds, infected with live strain PED virus (PEDV). Several gene ontology (GO) and differentially expressed gene (DEG) are also identified by RNA-seq. The analyzed transcriptome provides the 1805 DEGs and gene networks involving cellular processes. Between vaccinated and unvaccinated groups, there were 13 and 17 up- and down-regulated DEGs (2-fold; FDR < 0.05; P < 0.001), respectively, in PBMC of PEDV. Most of significant DEGs were involved in multiple cellular processes of cell growth and immune system. Thus, results from our current study indicate that DEG analysis of RNA-seq data help us better understand the precise mechanisms of PEDV in pig PBMC.