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To determine how age and distress are associated in individuals with disabilities, and how happiness and its components (meaning, pleasure, and engagement) mediate or moderate this relationship.These were cross-sectional analyses of survey data from 508 community-dwelling adults with a variety of self-reported health conditions and functional disabilities. Measures included the Orientations to Happiness Questionnaire and items from the Behavior Risk Factor Surveillance System.Greater distress was associated with lower global happiness in both mediation and moderation models. The mediation model showed that middle-aged participants (age: 45–64) scored lowest in global happiness, and the effect of age on distress was partially mediated by happiness. None of the happiness components mediated the relationship of age on distress. The moderation model showed a significant interaction effect for age and global happiness on distress, where younger participants low on happiness were significantly more distressed. Of the three happiness components, only meaning was significantly associated with distress. There was a significant interaction between age and meaning, where participants who were younger and scored low on the meaning scale reported significantly higher distress.Findings from this study lay groundwork for the development of clinical interventions to address distress in individuals with functional disabilities. Middle-aged and younger people with disabilities may be particularly affected by lower levels of happiness and might benefit from psychological interventions that focus on increasing overall well-being and providing meaning and purpose in life.