When alarmed, a cottontail can run up to twenty miles per hour in a zigzag pattern to escape predators. Often, the cottontail runs to a protective location like a burrow or thicket. A cottontail may also freeze when danger lurks, and scrunch down to blend into its surroundings. When temperatures climb above eighty degrees Fahrenheit, the cottontails' activity level decreases significantly. Cottontails can breed at eighty days old, then mate again soon after giving birth.
Adults live to about two years old.
Cottontails are preyed upon by a number of predators, including golden and bald eagles, great horned owls, ferruginous hawks, badgers, coyotes, foxes, bobcats and humans. Rattlesnakes may prey on the young. In the American Southwest, Native Americans hunted or trapped cottontails for meat, sewed the furs into blankets, used the hide to make glue, and used individual hides to make pouches. A male's home range may be up to fifteen acres in size. A female's home range can be less than one acre.