Cape Girardeau is a city in Cape Girardeau and Scott Counties in the U.S. state of Missouri. At the 2020 census, the population was 39,540, making it the 17th-largest in the state. The city is one of two principal cities of the Cape Girardeau, MO-IL Metropolitan Statistical Area, which encompasses Alexander County, Illinois, Bollinger County, Missouri and Cape Girardeau County, Missouri and has a population of 97,517.