It is well known that the rate of ageing varies among individuals dependent on the genetic background. In the present study, we explore how Wolbachia infection (a common insect endosymbiont bacterium) and oxidative stress interact in ageing with respect to two different genetic backgrounds of Drosophila melanogaster. Naturally infected and cured lines of Drosophila are challenged with either paraquat or l‐arginine to generate two different types of oxidative stress. We first observe that removing Wolbachia infection shortens the lifespan in one genetic background but not in the other. Wolbachia infection only makes one of the genetic lines more sensitive to paraquat. However, only the line unaffected by Wolbachia in the paraquat treatment is protected by Wolbachia from l‐arginine induced stress. Hence, Wolbachia is modifying free radical defence via two different mechanisms dependent on the genetic background. This supports the idea that factors that can govern ageing (infection and oxidative stress) are not universal, but are specific to the genetic make‐up of an individual.