Opelousas is a small city in and the parish seat of St. Landry Parish, Louisiana, United States. It lies at the junction of Interstate 49 and U.S. Route 190. The population was 22,860 at the 2000 census. Although the 2006 population estimate was 23,222, a 2004 annexation should have put the city's population above 25,000. In the 2010 census, but the population shrank to 16,634. Opelousas is the principal city for the Opelousas-Eunice Micropolitan Statistical Area, which had an estimated population of 92,178 in 2008. Opelousas is also the third-largest city in the Lafayette-Acadiana Combined Statistical Area, which has a population of 537,947.At 7.5 square miles, Opelousas is the most densely populated incorporated city in Louisiana. Founded in 1720, Opelousas is Louisiana's third-oldest city. The city served as a major trading post between New Orleans and Natchitoches in the 18th and 19th centuries.