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Keystone Heights is a city located in southwestern Clay County, Florida, United States. It is the southwesternmost city in the Jacksonville, Florida Metropolitan Statistical Area, and is the principal city and primary economic driver of the Lake Region, a region in Florida consisting of southwestern Clay County and parts of Bradford, Putnam, and Alachua counties, known for its many lakes. The population of the city was 1,446 at the 2020 census, up from 1,350 at the 2010 census.