Immigrant Latinos frequently experience social isolation in their receiving communities. This paper investigates the prevalence of social isolation among immigrant workers in a new settlement area and delineates the association between social isolation and physical and mental health outcomes. Interviews were conducted in Spanish with immigrant Latino manual workers (N = 743) in western North Carolina. The CES-D and the SF-12 questionnaires assessed health outcomes. A social isolation scale was used to assess degree of social isolation. Nearly 1 in 5 workers (19.5 %) reported the highest level of social isolation. Social isolation was associated with higher depressive symptoms and poorer physical and mental health, related to quality of life. Social isolation is a common experience among immigrant Latinos that may have negative implications for physical and mental health. Community outreach efforts to minimize experiences of isolation may be useful in protecting immigrant physical and mental health.