Perceived social isolation—commonly known as loneliness—is a psychosocial stressor that is associated with increased mortality, opioid use, and precipitants of relapse among individuals with opioid use disorders (OUD). Despite its association with greater clinical severity among individuals with OUD, there are no efficacy trials of perceived social isolation interventions among individuals with OUD. Importantly, there are effective interventions that can decrease perceived social isolation; however, there are no fully-powered efficacy trials that have directly intervened on perceived social isolation among individuals with OUD. Cognitive-Behavioral Therapy for Perceived Social Isolation (CBT-PSI) addresses negative beliefs that perpetuate perceived social isolation, increase negative affect, and reduce one’s ability to engage in social activities. For an individual with OUD, this is critical as addressing cognitive biases, negative affect, and having a sense that one has and engages social support are key aspects of recovery. The proposed R01 tests the efficacy of this brief, telehealth-delivered, evidence-based intervention, CBT-PSI, to decrease perceived social isolation Participants will be recruited nationally and will be randomized to either (a) therapist-delivered CBT-PSI, (b) therapist- delivered Health Education, or (c) self-guided Health Education. Each intervention will occur across 6 sessions delivered/administered on a weekly basis. The specific aims are to: (1) assess group differences in perceived social isolation among individuals with OUD, (2) assess group differences in opioid use among individuals with OUD, and (3) assess the reciprocal relationship between opioid use and perceived social isolation. Additional outcomes of interest include mental health symptoms, and the quality and quantity of social interactions. Outcomes will be assessed post-treatment, 1-month post-treatment, 3-months post-treatment, and 6-months post-treatment. This project has