HIV-related stigma may influence ethical concerns in health disparity populations, particularly groups with histories of race, gender, and class oppression in medical research such as African American women. However, a dearth of research has examined how HIV-related stigma influences perceptions of the research process among African American women who participate in health research. The goal of the current study was to examine whether HIV-related stigma experienced on the micro-level, specifically internalized HIV-related stigma, is associated with reactions to research participation in 5 domains: attitudes toward participation, perceptions of research benefits, emotional reactions, perceived drawbacks of the research, and global evaluations of the research. We also examine whether internalized HIV-related stigma is associated with difficulty in answering questions related to sensitive topics. We found that women with higher levels of internalized HIV-related stigma reported more emotional reactions to research, perceived more drawbacks of the research, and expressed more difficulty in answering sensitive questions. Understanding how HIV-related stigma influences perceived risks and benefits of research participation may play an important role in guiding best practices for ethical engagement with HIV-positive African American women who participate in health research.