In addition to its health benefits, mindfulness has been theorized in classical contemplative frameworks to elicit self-transcendent experiences as a means of promoting universal love and compassion. Increasing feelings of love may be especially clinically relevant for the treatment of opioid misuse, in that addictive use of opioids dysregulates neurobiological processes implicated in the experience of love. Here we tested these hypotheses in a secondary analysis (n = 187) of data from a randomized clinical trial of Mindfulness-Oriented Recovery Enhancement (MORE) versus supportive psychotherapy for comorbid opioid misuse and chronic pain. At pre- and post-treatment, participants completed a measure of state self-transcendence immediately following a laboratory-based mindfulness task. Through 9-month follow-up, we assessed changes in universal love and opioid misuse. Participants also completed ecological momentary assessments of opioid craving during the 8-week study interventions and for the following month. Compared to supportive psychotherapy, participants in MORE reported significantly greater increases in mindfulness-induced self-transcendence, which mediated the effect of MORE on increased feelings of universal love. In turn, increases in universal love significantly predicted decreased opioid craving and lower odds opioid misuse through 1- and 9-month follow-ups, respectively. Findings suggest mindfulness-induced self-transcendence may promote feelings of universal love, with possible downstream benefits on reducing addictive behavior.