Introduction Multiple studies have suggested an association between cytomegalovirus (CMV) infection and essential hypertension (EH). MicroRNAs (miRNAs) play a critical role in the development of EH by regulating the expression of specific target genes. However, little is known about the role of miRNAs in CMV-induced EH. In this study, we compared the miRNA expression profiles of samples from normal and murine cytomegalovirus (MCMV)-infected C57BL/6 mice using high-throughput sequencing analysis. Methods We collected the thoracic aorta, heart tissues, and peripheral blood from twenty normal mice and twenty MCMV-infected mice. We identified differentially expressed miRNAs in the peripheral blood samples and predicted their target genes using bioinformatics tools. We then experimentally validated them using qRT-PCR and the target genes with double luciferase reporter gene assay. Results We found 118 differentially expressed miRNAs, among which 9 miRNAs were identified as potential MCMV infection-induced hypertension regulators. We then validated the expression of two candidate miRNAs, mmu-miR-1929-3p and mcmv-miR-m01-4-5p, using qRT-PCR. Furthermore, the dual-luciferase reporter gene assay revealed that the 3'-untranslated region (UTR) of endothelin A receptor (Ednra) mRNA contained a binding site for mmu-miR-1929-3p. Collectively, our data suggest that MCMV infection can raise the blood pressure and reduce mmu-miR-1929-3p expression in C57BL/6 mice. Moreover, we found that mmu-miR-1929-3p targets the 3'-UTR of the Ednra mRNA. Conclusion This novel regulatory axis could aid the development of new approaches for the clinical prevention and control of EH.