Biological invasions by exotic species impose substantial ecological, economic and social costs worldwide, being a major threat to biodiversity conservation. Because not all individuals introduced in the new environments become successful invaders, the identification of factors underlying variation in invasion success would be essential for evaluating invasion risk. Here, we test several host–parasite hypotheses accounting for invasion success of house sparrows Passer domesticus in Peru. According to the Enemy Release Hypothesis, invasive house sparrows from Peru showed lower prevalence and genetic diversity of haemosporidian parasites than sparrows from their natural range (Spain), indicating that the release from their natural parasites may have favoured the spread of sparrows in the new area of occurrence. We also showed that Peruvian sparrows had larger uropygial glands and higher anti-bacterial activity in its secretion than sparrows from Spain, suggesting selection in defensive mechanisms driven by pathogens when colonizing new environments. Finally, we showed that uninfected sparrows had larger uropygial glands and higher anti-bacterial activity than malaria-infected house sparrows, implying that uropygial gland secretions may act as a defensive mechanism against haemosporidian infections. Alternatively, a condition-dependent trade-off exists between synthesis of uropygial secretion and immune response. These outcomes provide essential information for identifying potential invaders and designing interventions.