Objective: Gratitude, or thankfulness for positive aspects of life, is related to psychosocial well-being and decreased psychopathology, and may reduce suicide risk. We explored four potential hypotheses purported to explain the beneficial outcomes of gratitude (schematic, positive affect, broaden-and-build, and coping), hypothesizing that hopelessness (schematic), depression (positive affect), social support (broaden-and-build), and substance use (coping) would mediate the gratitude-suicide linkage. Participants: 913 undergraduate students from a mid-size, southeastern U.S. university. Methods: Respondents completed online self-report questionnaires including the Suicidal Behaviors Questionnaire-Revised, Gratitude Questionnaire, Beck Hopelessness Scale, Beck Depression Inventory, Duke Social Support Index, Alcohol Use Disorders Identification Test, and Drug Abuse Screening Test. Results: Supporting theory and hypotheses, gratitude was related to less suicide risk via beneficial associations with hopelessness, depression, social support, and substance misuse. Conclusions: The linkage between gratitude and suicide risk appears to be predicated on the beneficial association of gratitude to negative mood and interpersonal functioning.