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The global literature has revealed a potential negative impact of social stigma on both physical and mental health among stigmatized individuals; however, the mechanisms through which social stigma affects the individual’s quality of life and mental health are not well understood. This research simultaneously examines the relationships of several determinants and mediating factors of psychological distress and quality of life. Data were collected through a cross-sectional survey among 1006 adult (predominantly male) rural-to-urban migrants in 2004–2005 in Beijing, China. Participants reported on their perceived social stigma, discriminatory experiences in daily life, preparation for migration, discrepancy between expectation and reality, coping with stigma-related stress, psychological distress, and quality of life. Structural equation modeling was performed. We found that perceived social stigma and discriminatory …