Background: Cognitive behavioral therapy for adherence and depression (CBT-AD) performed by clinical psychologists is an effective treatment for improving the depression in people living with HIV (PLWH). However, because access to clinical psychologists is limited in most clinics, CBT-AD is rarely performed for PLWH in Korea. This pilot study evaluates whether CBT-AD can be effectively performed by a nurse trained and supervised by a clinical psychologist, with a view to the wider provision of CBT-AD. Materials and Methods: One clinical psychologist developed manuals, educated and supervised one nurse. PLWH with depression or adherence to self-reported antiretroviral therapy <90% were enrolled, and CBT-AD was conducted once weekly for 12 sessions. PLWH were assessed for adherence by visual analog scale, Beck depression inventory (BDI) for depression, PozQoL for quality of life, and Berger’s 40-item stigma scale for stigma at baseline, after the 6th, 12th session, at 4-, and 8-months after CBT-AD. Acceptability for PLWH and feasibility for providers were evaluated through surveys. Results: Five male PLWH have completed the study protocols (mean age 29.2 years). All study participants showed improving depression (mean BDI at baseline 33.0 ± 7.0, and after the 12th session 13.4 ± 3.5), and the effect was maintained at the 8-month follow-up (BDI 15.4 ± 6.4). Quality of life showed a tendency to improve (mean PozQoL at baseline 28.0 ± 7.7, after 12th session 36.8 ± 4.4, and at the 8-month follow-up 38.2 ± 7.9), but stigma did not show clear improvement (Berger’s 40-item stigma scale at baseline 121.0 ± 3.9, after 12th session 107.6 ± 8.8. and at the 8-month follow-up 107.6 ± 5.0). All study participants received great help from CBT-AD and expressed their desire to continue. All providers agreed that nursedelivered CBT-AD could be implemented in routine clinical practice. Conclusion Our findings suggest that a nurse-delivered CBT-AD could be feasible and acceptable for PLWH through structured interventions. It has been shown to have the potential to help PLWH, especially for their depression and quality of life.