Rodents play a key role in forest regeneration by dispersing seeds and interspecific differences in seed preferences could have important consequences for forest growth. The White-footed Mouse (Peromyscus leucopus) and Deer Mouse (Peromyscus maniculatus gracilis) are 2 closely related species that can exploit Red Oak (Quercus rubra) acorns but may display different preference levels due to the high tannin concentration present in these acorns. Here we investigated how White-footed Mice and Deer Mice differ in their ability to exploit Red Oak acorns. We conducted a cafeteria-style experiment where we offered mice (n = 61) acorns of Red Oak and Bur Oak (Q. macrocarpa; control seed with lower tannin levels) and video-recorded their preference and the acorn fate (consumed or cached). Using mixed-effects models, we found that both mouse species selected and consumed Bur Oak acorns at a high rate; however, White-footed Mice were 6.67 times more likely to select and consume Red Oak acorns than Deer Mice. Furthermore, White-footed Mice tended to cache Red Oak acorns near the surface where there is a higher chance of germination, while they usually consumed Bur Oak acorns. Our results suggest that Red Oaks have a better strategy for avoiding predation than Bur Oaks (i.e., high tannin levels leading to caching), and the strong interaction between the White-footed Mouse and Red Oak might be an important mechanism behind the current range expansion of both species in response to climate change.