Persons living with HIV (PLWH) often seek complementary treatments to improve their overall health and well-being. Reiki, an ancient healing practice, has been found to be effective in reducing symptoms of stress, anxiety, pain, and depression. The purpose of this pilot study was to evaluate the effectiveness of Reiki as a complementary treatment for PLWH. Using a two-group mixed-methods experimental design, 37 participants were randomized to either a 6-week Reiki with Music Group or a Music Only Group. Self-reported and physiologic measures were obtained at baseline, 6 weeks, and 10 weeks. Significant improvements in relief of pain and stress in those receiving RMG were found. At the 6-week assessment, semi-structured interviews were conducted with all participants. Qualitative findings indicated that Reiki and music therapy helped reduce stress, anxiety, and depression. Evidence-based data regarding the effectiveness of Reiki will help nurses help patients better manage HIV-related symptoms.