Opelika is a city in and the county seat of Lee County in the east-central part of the U.S. state of Alabama. It is a principal city of the Auburn-O…Opelika is a city in and the county seat of Lee County in the east-central part of the U.S. state of Alabama. It is a principal city of the Auburn-Opelika Metropolitan Area. As of the 2020 census, the population of Opelika is 30,995, an increase of 17.1 percent from the 2010 Census where the population was 26,477. The Auburn-Opelika, AL MSA with a population of 150,933, along with the Columbus, Georgia metropolitan area, comprises the Greater Columbus combined statistical area, a region home to 501,649 residents.