Abstract.Background: Porcine circovirus 2 causes different clinical syndromes resulting in a significant economic loss in thepork industry. Three pigs with unexplained cardiac and multi-organ inflammation that tested negative for PCV2 andother known porcine pathogens were further analyzed.Methods: Histology was used to identify microscopic lesions in multiple tissues. Metagenomics was used to detectviral sequences in tissue homogenates. In situ hybridization was used to detect viral RNA expression in cardiac tissue.Results: In all three cases we characterized the genome of a new circovirus we called PCV3 with a replicase and capsidproteins showing 55 and 35 % identities to the genetically-closest proteins from a bat-feces associated circovirus andwere even more distant to those of porcine circovirus 1 and 2. Common microscopic lesions included non-suppurativemyocarditis and/or cardiac arteriolitis. Viral mRNA was detected intralesionally in cardiac cells. Deep sequencing intissues also revealed the presence of porcine astrovirus 4 in all three animals as well as rotavirus A, porcine cytomegalovirusand porcine hemagglutinating encephalomyelitis virus in individual cases.Conclusion: The pathogenicity and molecular epidemiology of this new circovirus, alone or in the context ofco-infections, warrants further investigations.