Background: The microsporidian Nosema whitei is a natural parasite of the red flour beetle, Tribolium castaneum. The results of a previous study showed that, during co-evolution of the two species in the laboratory, host populations maintained elevated levels of heterozygosity. Hypothesis: Heterozygote advantage accounts for the maintenance of high levels of host heterozygosity during co-evolution with the parasite. Reduced heterozygosity of the beetle will lead to a decrease in resistance against parasite infection. Methods: In two experiments, we tested for (a) the effect of inbreeding and (b) the effect of inbreeding and outcrossing on the beetle's resistance to infection, in relation to effects on egg hatching success, development time, and reproductive success. Results: Inbreeding reduced egg hatching success, prolonged development time, and resulted in lower reproductive success. Outcrossing shortened development time, while we did not find evidence for heterosis for reproductive success. We were unable to detect an effect of changes in heterozygosity on overall resistance to parasitism. The effect of inbreeding on development time did, however, influence parasite-induced mortality profiles: the prolonged development time, resulting from inbreeding, led to higher mortality in earlier developmental stages, but left the overall mortality rate unchanged. Hence, we conclude that heterozygosity is not a principal determinant of the beetle's resistance to infection by N. whitei.