HIV is a highly stigmatized and stressful condition for people with HIV (PWH). As a country heavily influenced by religion, especially Buddhism, we explore how the perceived stress from HIV stigma interacts with the mediator of mindfulness on PWH in Myanmar. From January to July 2020, a sample of 248 eligible PWH was recruited by quasi-random sampling methods from a private Facebook group in Myanmar. Data on demographics, HIV stigma, mindfulness, and perceived stress were collected. The bias-corrected percentile bootstrap method was used to test multiple mediation analyses. The path from perceived HIV stigma to perceived stress (direct effect b 5 0.16) and the mediating effect of mindfulness on that stress were significant (indirect effect accounts for 45.15% of total effect). The findings indicate that interventions enhancing mindfulness-based practice should be considered to reduce HIV stigma and, therefore, lower perceived stress among PWH in Myanmar.