Objective To investigate the in vivo histological distribution of sialic acid receptors in dogs and itsassociation with the susceptibility to canine influenza virus H3N2. Methods Different organs and tissues were collectedfrom healthy English Springer Spaniel dogs. The type and histologic distribution of SAα2,6Gal and SAα2,3Gal linkage inthese organs were determined using a lectin-based histochemistry method. Organs from dogs artificially infected with H3N2virus were also collected, and were examined by immunohistochemistry to investigate the distribution of virus in vivo.Results SAα2,3Gal and SAα2,6Gal receptors coexisted in most organs and tissues, but also demonstrated differentialexpression in some organs. Among the different organs examined, SAα-2,6Gal receptors generally demonstrated a broaderexpression profile and higher level of expression than SAα-2,3Gal receptors. The in vivo tissue distribution of H3N2 virus inartificially infected dogs was largely consistent with the tissue distribution of sialic receptors, although in a small number oftissues this relationship was not observed. Conclusions Receptors for avian and human influenza virus are widelyexpressed in various tissues and organs of dogs, providing a molecular basis for co-infection of avian and human influenza virus.