Background Support groups’ important role in destigmatizing HIV/AIDS and addressing social-psychological needs of persons living with HIV (PLWH) is well documented. However, the impact of support groups in economic activities is less studied. Our study compares HIV- and non-HIV- support groups in providing social-psychological and economic empowerment for PLWH or at-risk groups in rural Kenya. Methods We recruited 72 participants in 12 support groups (42 women, 30 men; 6 HIV, 6 non-HIV). Interviews lasted 1.5–4 h. Participants were asked to describe the benefits and challenges of support groups. We used MAXQDA qualitative software. We used thematic analysis informed by Grounded Theory principles to develop themes. Results HIV- and non-HIV groups provided socio-psychological benefits to members. However, HIV groups engaged in community-based HIV testing promotion, and empowered members on fight HIV-stigma and to disclose HIV-status. HIV-groups—mostly donor-financed—had challenges related to financial mismanagement and lack of transparency of disbursements. Non-HIV groups—mostly micro-financing initiatives—offered financial assistance (e.g., school fees, hospital expenses), start-up capital for business projects, and improved the standard of living for members. Non-HIV-groups had challenges related to marital conflict and violence about finances, high rate of loan-default among members; and high direct (e.g., membership financial contribution, transport costs) and indirect (e.g., time commitments) costs of group participation. Conclusion HIV-support groups are underutilised in economic empowerment initiatives for PLWH, and face challenges of sustainability, in part due to poor leadership, financial mismanagement and high financial dependency on external funding. Non-HIV groups are underutilised as venues for community-based HIV prevention efforts. Before engaging in micro-finance activities, support groups should receive leadership and financial training to ensure their long-term sustainability and increase group effectiveness in uplifting the quality and standards of living for persons living with or at-risk for HIV in rural communities. Disclosure of interest statement This study was funded by the University of Wisconsin-Milwaukee College of Nursing Start-Up funds, U. S. A. No pharmaceutical grants were received in the development of this study.