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Santa Margarita is an unincorporated community located in San Luis Obispo County, California. It was founded in 1889 near Cuesta Peak and San Luis Obispo along today's State Route 58. The town's name comes from the Mexican Alta California land grant of Rancho Santa Margarita. It is home to the Santa Margarita de Cortona Asistencia site. For statistical purposes, the United States Census Bureau has defined Santa Margarita as a census-designated place (CDP). The population was 1,291 at the 2020 census.