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This study explored the factor structures, partial correlational, unique and indirect associations of meaning and purpose with depressive symptoms and suicide ideation in college students (n = 956) and adults with chronic illness (n = 346). Results showed that correlated two-factor models better captured (both absence and presence of) meaning and purpose, compared to the unidimensional models. Although meaning and purpose were strongly associated, they were differentially correlated with and predictive of mental health outcomes. On one hand, while absence of meaning was positively and moderately correlated with and predictive of depressive symptoms and suicide ideation, the associations of absence of purpose were, albeit similar, weak. On the other hand, presence of meaning was negatively and moderately correlated with and predictive of depressive symptoms and suicide ideation, and the presence of purpose only predicted suicide ideation in negligible amounts among students but not adults with chronic illness. In both samples, absence of meaning and purpose were indirectly and positively related to suicide ideation through their positive associations with depressive symptoms; whereas presence of meaning, but not presence of purpose, was indirectly and negatively associated with suicide ideation through its negative associations with depressive symptoms. Conceptual and counseling implications are discussed. [ABSTRACT FROM AUTHOR]