1. Acute activation of the immune system often initiates a suite of behavioural changes. These ‘sickness behaviours’—involving lethargy and decreased activity—may be particularly costly on invasion fronts, where evolutionary pressures on dispersal favour individuals that move large distances. 2. We used a combination of field and laboratory studies to compare sickness behaviours of cane toads from populations differing in invasion history. To do this we stimulated immune system activation by injecting lipopolysaccharide (LPS) to mimic bacterial infection. 3. We predicted that LPS would result in less severe sickness behaviour in toads from invasion-front populations because they had undergone selection for rapid and sustained dispersal (activities in conflict with lethargy and decreased activity). 3. Contrary to our prediction, LPS injection caused a greater reduction in dispersal-relevant traits in invasion-front individuals than in conspecifics from the range core. 4. Our data suggest that the rapid invasion of cane toads through tropical Australia has seen an evolutionary shift in the magnitude of sickness behaviour elicited by pathogen infection. The increased sickness behaviour among invasion-front toads suggests a shift away from pathogen tolerance (seen in range-core populations) towards resistance to pathogen attack. But as a consequence, when pathogens do become successfully established, toads from invasion-front populations may have less capacity to tolerate their ill-effects.