Head and body length of Peromyscus species range from 70-170 mm and tail lengths are 40-205 mm. There are 2 subgenera and 55 species.

P. gossypinus has soft dense fur and large ears which are covered with fine hairs. The tail is about one third the length of the total length of this mouse, and is also covered with fine hairs. Females have four or six mammae.

The preferred habitat is deep woodlands and brushy areas. Several nest are built each year and are line with soft down from plants or other materials which are shredded. Once a nest is soiled it is abandoned and another is constructed. P. gossypinus is primarily nocturnal and active year round, though periods of torpor occur for several hours, during which time there is a drop in body temperature.

P. gossypinus breeds throughout the year with lower productivity during the summer months. Estrous cycles last an average of 7 days, gestation periods range from 21-27 days for non-lactating females and as much as 40 days for lactating females.Overall weights for newborn Peromyscus is 2.2 grams and the eyes open at about 2 weeks of age. Mean litter size for the species is 3.4 young. Most are weaned at 3-4 weeks old and stay with their mother for another month.

P. gossypinus is found in SE USA, from SE Oklahoma, extreme S Illinois and SE Virginia, southwards, skirting the S Appalachians, to E Texas, the Gulf States, and peninsular Florida.