Eastern cottontail rabbits are adults at 4 months, and it is not advisable to mate immediately at this time, which may cause premature birth and dystocia of female rabbits. Therefore, it is recommended to breed after 6 months of age. Rabbits do not have a fixed estrus time, and they can mate and breed all year round, but they should avoid high and low temperature seasons to ensure the survival of their young.

The mating period of the Eastern Cottontail Rabbit is from February to September every year moon. Male rabbits will mate with more than one female rabbit. Female rabbits can give birth two to four times a year, with up to nine litters at a time. Female rabbits build their nests on the ground with grass and fur, and can mate again immediately after it takes effect. The cubs are weaned from milk when they are three weeks old, they are allowed to leave the nest after seven weeks, and the next generation will be reproduced after three months. The average life expectancy of wild eastern cottontail rabbits is only 2 years, and the lifespan in captivity will be longer.