Emerging research suggests that prescription opioid craving is associated with negative mood and depression, but less is known about cognitive factors linking depressive symptoms to opioid craving among adults with chronic pain. The present cross-sectional study examined thought suppression as a mediator of the relation between depression and prescription opioid craving in a sample of chronic pain patients receiving long-term opioid pharmacotherapy. Data were obtained from 115 chronic pain patients recruited from primary care, pain, and neurology clinics who had taken prescription opioids daily or nearly every day for ≥90 days prior to assessment. In this sample, 60 % of participants met DSM-IV criteria for current major depressive disorder. Depressed mood (r = .36, p < .001) and thought suppression (r = .33, p < .001) were significantly correlated with opioid craving. Multivariate path analyses with bootstrapping indicated the presence of a significant indirect effect of thought suppression on the association between depressed mood and opioid craving (indirect effect = .09, 95 % CI .01, .20). Sensitivity analyses showed a similar indirect effect of suppression linking major depressive disorder diagnosis and opioid craving. Attempts to suppress distressing and intrusive thoughts may result in increased craving to use opioids among chronic pain patients with depressive symptoms. Results highlight the need for interventions that mitigate thought suppression among adults with pain and mood disorders.