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. The city is one of two principal cities of the Cape Girardeau-Jackson, 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.