Spotted skunks are largely nocturnal and are active all year. The omnivorous diet consists mainly of vegetation and insects in the summer and of rodents and other small animals in the winter. The white-plumed tail is used to warn other animals that spotted skunks should not be molested. If, however, the sudden erection of the tail is not sufficient deterrence, Spilogale may stand on its forefeet and sometimes even advance toward its adversary. In spring the males wander over an area of about 5-10 sq km, but females have smaller ranges.
Spotted skunks are very playful with one another.
As many as eight individuals sometimes share a den. Populations in South Dakota and Florida apparently mate mainly in March and April. Implantation of the fertilized eggs in the uterus occurs only 14-16 days later, and births take place in late May and June. Pregnancy is estimated to last 50-65 days. Populations farther to the west mate in September and October, but implantation is delayed until the following March or April, and births occur from April to June.