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Data on empirical associations between religious variables and health outcomes are needed to clarify the complex interplay between religion and mental health. The aim of this study was to determine whether associations with health variables are primarily attributable to explicitly religious aspects of spiritual well-being (SWB) or to “existential” aspects that primarily reflect a sense of satisfaction or purpose in life. Three hundred forty-five pairs of twins from the Vietnam Era Twin Registry completed a diagnostic interview and questionnaires containing the 2-factor SWB Scale and general health items. Observed associations between SWB and health outcomes were uniquely explained by the SWB subscale of existential well-being, with much less of a unique explanatory contribution from religious well-being or “spiritual involvement.” We concluded that studies of SWB and health should continue to distinguish between explicitly religious variables and others that more closely approximate the psychological construct of personal well-being.