Key Cave National Wildlife Refuge protects the only known population of the Alabama cavefish. This blind, colorless fish lives in underground pools within the cave. The Alabama cavefish is considered one of the rarest vertebrates in the world due to its limited habitat range and the infrequent sightings during past survey efforts. These surveys did indicate that offspring are occurring. Another endangered species, the Gray bat, provides guano that is a food resources for the copepods, isopods, and amphipods living in Key Cave. In turn, those animals are what the cavefish feed on.
In addition, several bird species of management concern use the refuge's grasslands. These species include grasshopper sparrows, dickcissels, northern harriers, short-eared owls, loggerhead shrikes, and northern bobwhites.