Pathogenic microbes constitute a menace for the health of animals. In consequence, many animals have evolved highly efficient antimicrobial defences to fight against infections. The uropygial gland is an organ that produces an oily substance with antimicrobial properties that it is smeared on the plumage during preening. The volume of the uropygial gland secretion is related to the size of the gland. It has been proposed that the size of the gland varies as a consequence of divergent selection by pathogens on their hosts. The concentration of pathogenic microbes may differ between different areas. Hence, the volume and antimicrobial properties of the uropygial gland secretion could change between different environments. Here, we analysed the volume and activity of uropygial secretion of different populations of house sparrows (Passer domesticus). Our results showed that the volume and activity of this secretion is negatively related with the concentration of microorganisms in feathers. These outcomes suggest that the uropygial gland secretion plays a specific role in the regulating the concentration of microorganisms in the feather, which may affect the prevalence of malaria infection.