Immune activity is variable within and among vertebrates despite the potentially large fitness costs of pathogens to their hosts. From the perspective of life history theory, immunological variability may be the consequence of counterbalancing investments in immune defense against other expensive physiological processes, namely, reproduction. In the present study, we tested the hypothesis that immune defense among captive-bred, disease-free Peromyscus mice would be influenced by their reproductive life history strategies. Specifically, we expected that small species that reproduce prolifically and mature rapidly (i.e., fast pace of life) would favor inexpensive, nonspecific immune defenses to promote reproductive proclivity. Alternatively, we expected that large species that mature slowly and invest modestly in reproduction over multiple events (i.e., slow pace of life) would favor developmentally expensive, specific immune defenses and avoid cheap, nonspecific ones because such defenses are predisposed to self-damage. We found that species exhibited either strong ability to kill (gram-negative) bacteria, a developmentally inexpensive defense, or strong ability to produce antibodies against a novel protein, a developmentally expensive defense, but not both. Cell-mediated inflammation also varied significantly among species, but in a unique fashion relative to bacteria killing or antibody production; wound healing was comparatively similar among species. These results indicate that Peromyscus species use immune strategies that are constrained to a dominant axis, but this axis is not determined solely by reproductive pace of life. Further comparisons, ideally with broader phylogenetic coverage, could identify what ecological and evolutionary forces produce the pattern we detected. Importantly, our study indicates that species may not be differentially immunocompetent; rather, they use unique defense strategies to prevent infection.