ABSTRACT: Objective: Few studies have examined relations between one important aspect of spiritual/religious functioning—spiritual distress—and pain-related outcomes, and none has examined how spiritual distress and depression conjointly relate to chronic pain. The goal of the present study, then, was to examine veterans’ spiritual distress as a predictor of two aspects of chronic pain, catastrophizing and interference, testing a mediational model of depression. Design: Four hundred thirty-six patients seeking treatment in a chronic pain management clinic responded to a mailed survey assessing demographics, spiritual distress, depression, pain catastrophizing, and pain interference. Setting: Participants were drawn from a list of patients enrolled in a chronic pain rehabilitation program at a large Midwestern Veterans Affairs health care system. Subjects: Participants were 436 veterans seeking chronic pain rehabilitation. The sample was predominantly Caucasian and male. Methods: Survey data were subjected to mediational analysis, assessing both direct effects of spiritual distress on pain outcomes and indirect effects of spiritual distress through depression. Results:  Results showed that spiritual distress was moderately strongly related to both pain outcomes. Further, depression mediated links between spiritual distress and pain catastrophizing (partially) and interference (fully). Conclusions: These results have implications for further research in spiritually integrated care as a component of holistic, integrative approaches to the management of chronic pain.