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This study examined whether mindfulness strategies (e.g., acting nonjudgmentally with awareness and attention to present events) were effective in mitigating the associations among school-based victimization related to ethnicity and sexual orientation, well-being (i.e., depressive symptoms and self-esteem), and grade point average (GPA). The U.S.-based sample included 236 Latina/o sexual minority students, ranging in age from 14 to 24 years (47% were enrolled in secondary schools, 53% in postsecondary schools). Results from structural equation modeling revealed that ethnicity-based school victimization was negatively associated with GPA but not well-being. However, sexual orientation-based victimization was not directly associated with well-being or GPA. Mindfulness was positively associated with well-being but not GPA. High levels of mindfulness coping were protective when the stressor was sexual orientation-based victimization but not ethnicity-based school victimization. These findings contribute to a growing literature documenting the unique school barriers experienced by Latina/o sexual minority youth and highlight the promising utility of mindfulness-based intervention strategies for coping with minority stress.