Long‐term calorie restriction (CR) has numerous benefits; however, effects of CR on susceptibility to intact pathogens are not well understood. Because CR enhances immune function of laboratory mice (Mus musculus), it was hypothesized that mice subjected to CR would be less susceptible to experimental infections of the intestinal parasite Heligmosomoides bakeri. Furthermore, because H. bakeri must combat a greater host immune response by CR mice compared to fully fed mice, it also was also hypothesized that (i) worms living in CR hosts would have lower reproduction than worms from ad libitum‐fed mice, and (ii) CR mice would have a more female‐biased sex ratio as male worms may be more vulnerable to host immune response than female worms. Mice were subjected to CR for 6.7 months and were then infected with H. bakeri for one additional month. As expected, CR mice had equal or enhanced immune response (eosinophils and immunoglobin G1 production) to H. bakeri infection compared to ad libitum‐fed mice, and CR mice harbored a more female‐biased sex ratio than ad libitum‐fed mice. Contrary to predictions, CR mice had more worms than ad libitum‐fed mice and the worms from CR mice produced more eggs than worms from ad libitum‐fed mice. These data indicate that, despite the evidence that long‐term CR enhances traditional measures of immune function, CR may actually increase susceptibility to intact parasite infection. Furthermore, changes in worm reproduction and differential survival of male vs. female worms may influence host–parasite transmission dynamics during long‐term host CR.