Background: The relationships between opioid use disorder (OUD), chronic pain, and mental health distress are complex and multidirectional. The objective of this exploratory study was to examine the relationship between mental health conditions and Chronic pain severity and interference among patients stabilized on either buprenorphine or methadone. Methods: We report baseline data from a randomized trial of a mind-body intervention conducted at 5 outpatient clinics that provided either buprenorphine or methadone treatment. Validated scales were used to measure substance use, mental health distress, and pain severity and interference. Statistical analyses examined the relationship between mental health conditions and pain severity and interference. Results: Of 303 participants, 57% (n = 172) reported Chronic pain. A total of 88% (n = 268) were prescribed buprenorphine. Mental health conditions were common, with one-quarter of the sample screening positive for all 3 mental health conditions (anxiety, depression, and posttraumatic stress disorder [PTSD]). Compared to participants without Chronic pain, participants with Chronic pain were more likely to screen positive for moderate-severe anxiety (47% vs 31%); moderate-severe depression (54% vs 41%); and the combination of anxiety, depression, and PTSD (31% vs 18%). Among participants with Chronic pain, mental health conditions were associated with higher pain interference. Pain severity was higher among participants with mental health conditions, but only reached statistical significance for depression. Pain interference scores increased with a higher number of co-occurring mental health conditions. Conclusions: Among individuals stabilized on either buprenorphine or methadone, highly symptomatic and comorbid mental health distress is common and is associated with increased pain interference. Adequate screening for, and treatment of, mental health conditions in patients with OUD and Chronic pain is needed.