Coevolution among predator-prey interactions is a common phenomenon and often leads to a diverse series of physiological and behavioral adaptations associated with avoiding predation and, on the part of predators, overcoming those defenses. Pit viper rattlesnake and small mammal prey share a long evolutionary history that has resulted in the coevolution of traits. Those traits being mammal specific venom toxicity in rattlesnakes and an innate physiological venom resistance among mammal prey. Snake venom metalloproteinase (SVMP) are a class of venom toxins that are found in large quantities across viperid snakes and a cause severe damage to blood and endothelial cells, facilitating the spread of other venom toxins. Resistant mammals are expressing snake venom metalloproteinase inhibitors (SVMPIs) that irreversibly bind to SVMPs, preventing the destruction of cells and mitigating the spread of venom toxins throughout the prey’s body. My research explored the variation in venom resistance among California ground squirrels (Otospermophilus beecheyi) and Bryant’s woodrats (Neotoma bryanti) when tested against the venom of Southern Pacific rattlesnakes (Crotalus oreganus helleri) and Red Diamond rattlesnakes (Crotalus ruber) across four sites in San Diego County. I aimed to understand venom resistance variation between species, populations and assessed these populations for signals of local adaptation. The results of this study demonstrate that mammal venom resistance across mammal species is not significantly different, however, mammals are expressing more venom resistance towards Southern Pacific rattlesnakes. Each population of mammals showed varying levels of venom resistance, however, there was no signal of local adaptation by either the mammal or the snake species. Additionally, previous research has suggested that there is a physiological constraint to mammals producing SVMPIs. I assessed and quantified mammal body condition in order to further understand the relationship between mammalian physiological function and venom resistance. Results of this study suggest that mammals that are in poor body condition are expressing lower venom resistance levels than mammals in better body condition.