Invasive species are of increasing conservation and economic concern, yet mechanisms underlying invasions remain poorly understood. We propose that variation in immune defences might help explain why only some introduced populations become invasive. Introduced species escape many of their native diseases, but also face novel pathogens that can induce costly, and sometimes deadly, immune responses in naïve hosts. Therefore, favouring less resource-demanding and dangerous defence mechanisms and allocating a greater proportion of resources to growth and reproduction should favour invasion. Specifically, we argue that successful invaders should reduce costly systemic inflammatory responses, which are associated with fever and metabolic and behavioural changes, and rely more heavily on less expensive antibody-mediated immunity. Here we provide supporting arguments for this hypothesis and generate predictions that are testable using tools from the growing field of ecological immunology.