Host immune traits arise from both genetic and environmental sources of variation. When immune traits have a strong genetic basis, the presence and severity of disease in a population may influence the distribution of those traits. Our study addressed how two immune‐related traits (gut penetrability and the hemocyte response) are shaped by genetic and environmental sources of variation, and how the presence of a virulent disease altered the relative frequency of these traits in natural populations. Daphnia dentifera hosts were sampled from five Indiana lakes between June and December 2017 before and during epidemics of their fungal pathogen, Metschnikowia bicuspidata . Collected Daphnia were experimentally exposed to Metschnikowia and assayed for their gut penetrability, hemocyte response, and multi‐locus genotype. Mixed‐effects models were constructed to partition variance in immune traits between genetic and environmental sources. We then isolated the genetic sources to produce genotype‐specific estimates of immune traits for each multi‐locus genotype. Finally, we assessed the relative frequency and dynamics of genotypes during epidemics and asked whether genotypes with more robust immune responses increased in frequency during epidemics. Although genotype was an important source of variation for both gut penetrability and the hemocyte response, environmental factors (e.g., resource availability, Metschnikowia prevalence, and co‐infection) still explained a large portion of observed variation, suggesting a high degree of flexibility in Daphnia immune traits. Additionally, no significant associations were detected between a genotype's immune traits and its frequency in a population. Our study highlights the power of variance partitioning in understanding the factors driving variation in Daphnia traits and motivates further research on immunological flexibility and the ecological drivers of immune variation.