When three to four months old, young opossums begin to look for their own food and care for themselves. Soon they stop nursing, but they may stay with the female a few weeks longer. Six to nine young usually survive to fend for themselves. Females may bear a second litter, breeding again from mid-May to early July. At least two weeks pass between weaning of the first litter and birth of the second, as the female is not sexually receptive while still nursing.
Females can breed when they are a year old.
In fall and winter, opossums devote almost twice as much time to feeding and improving their nests as they do the rest of the year. Opossums do not hibernate, but may den up during cold or snowy periods. Although they add a layer of fat, they do not grow a winter pelt, and their fur is poor insulation. Pennsylvania is near the species' northern limit, and many opossums lose the tips of their ears and tails to frostbite. Ticks, fleas, cestodes and nematodes parasitize opossums, and the species is preyed on by foxes, bobcats, hawks and owls.