New England's only native rabbit, the New England cottontail looks nearly identical to the eastern cottontail, which was introduced to the region as a game species in the early 1900s. Similar in size with grayish brown fur, the two can only be distinguished with certainty by examining skulls or conducting DNA analysis. The New England cottontail began to decline during the 20th century due to a loss of its early successional forest habitat, often called thickets, compounded by competition from deer and eastern cottontail.

In 2006, the New England cottontail became a candidate for listing under the Endangered Species Act. A strong partnership of state and federal biologists, private landowners, tribes, foresters, hunters, conservation organizations and others began implementing conservation actions to halt population declines and improve the species' status, leading to a U.S Fish and Wildlife Service determination in 2015 that the New England cottontail did not need federal listing. The Service continues to support New England cottontail conservation efforts, including through the Great Thicket National Wildlife Refuge. Rather than protecting land in a single location, the Service aims to acquire up to 15,000 acres of shrubland and young forest habitat for the refuge from willing landowners across focal areas in New York and New England.