High Quality Content by WIKIPEDIA articles! Opelousas is a city in and the parish seat of St. Landry Parish, Louisiana, United States. It lies at the juncture 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 put the city's population above 25,000. 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 3rd largest city in the Lafayette-Acadiana Combined Statistical Area, which has a population of 537,947.