Hunting: The Lower Keys rabbit was once hunted for food and fur, and even though it's now officially protected, some illegal hunting still occurs.
Disease: The Lower Keys rabbit is susceptible to a variety of diseases, including tularemia, which is a bacterial disease that can be fatal to rabbits. Tularemia is spread by ticks, and the Lower Keys rabbit's habitat is home to many ticks.
Predation: The Lower Keys rabbit is preyed upon by a variety of animals, including snakes, owls, and hawks. The introduction of non-native predators, such as cats, has also contributed to the decline of the Lower Keys rabbit.
Climate change: Climate change is also a major threat to the Lower Keys rabbit. Rising sea levels are inundating the rabbit's habitat, and more extreme weather events, such as hurricanes, are destroying its food and shelter.