Immune function can vary based on availability of resources, and most studies of such influences have focused on the co-investment of energy into immune and other physiological functions. When energy resources are limited, trade-offs exist, which can compromise immunity for other functions. As with energy, water limitation can also alter various physiological processes, yet water has received little consideration for its possible role in modulating immune functions. We examined the relationship between immunocompetence and hydration state using the western diamond-backed rattlesnake (). This species is known to undergo substantial seasonal fluctuations in water availability with extreme limitations during the hot-dry season. We collected blood samples from free-ranging to compare osmolality and innate immune function (lysis, agglutination and bacterial growth inhibition) during the milder and relatively moister early spring season, the hot-dry season and the hot-wet season. To isolate effects of dehydration from other possible seasonal influences, we complemented this field study with a laboratory study in which we withheld food and water from individually housed adult for up to 16 weeks. We collected blood samples from each snake as it dehydrated and collected a final sample after the snake was given water at the end of the experiment. Our results demonstrate that experience significant dehydration during the hot-dry season, and that, in general, innate immune function is highly correlated with osmolality, whether natural or artificially manipulated.