The resource allocation hypothesis predicts that reproductive activity suppresses immunocompetence; however, this has never been tested in an endemic disease system with free-ranging mammals. We tested the resource allocation hypothesis in wild deer mice (Peromyscus maniculatus) with natural exposure to Sin Nombre Virus (SNV). Immunocompetence was estimated from the extent of swelling elicited after deer mice were injected with phytohemagglutinin (PHA); swelling is positively correlated with immunocompetence. After livetrapping deer mice, we determined their reproductive state and SNV infection status. Males were more likely to be seropositive for SNV than females (37% vs. 25%) and exhibited 10% less swelling after PHA injection. The swelling response of females differed with both infection status and reproductive condition. There was also a significant infection status by reproductive condition interaction: nonreproductive, seropositive females experienced the least amount of swelling, whereas females in all other categories experienced significantly greater swelling. The swelling response of males differed with both SNV infection status and reproductive condition, but there was no significant infection status by reproductive condition interaction. Seronegative males elicited greater swelling than seropositive males regardless of reproductive status. In contrast to the resource allocation hypothesis, these results do not indicate that reproductive activity suppresses immunocompetence of deer mice but rather suggest that chronic SNV infection reduces immunocompetence. Sex-based differences in swelling indicate that SNV modulates the immune system of female deer mice differently than it does that of males, particularly during reproduction. We propose that differences in resource allocation between males and females could result from inherent sex-based differences in parental investment.