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Background Human immunodeficiency virus (HIV) related depression has seriously affected the quality of life and treatment outcomes of patients living with HIV (PLWH), which has become a hot topic in recent years. This study aims to discover the main keywords, predict frontier topics, and give meaningful suggestions for researchers by bibliometric analysis. Methods Publications between 1999 and 2022 on depression in HIV/AIDS were searched in the Web of Science core collection. Microsoft Excel 2010 and VOSviewer were utilized to key contributors (e.g., authors, journals, institutions, and countries). VOSviewer and CiteSpace were used to analyze the knowledge evolution, collaborative maps, hot topics, and keywords trends in this field. Results In total, 8,190 publications were included in the final analysis. From 1999 to 2021, the number of published articles roughly presents a steadily increasing trend. The United States, South Africa, and the United Kingdom were three key contributing countries/regions to this field. University Calif San Francisco (United States), University Calif Los Angeles (United States), and Johns Hopkins University (United States) were three key contributing institutions. Safren, Steven A. was the most productive and highest cited author. AIDS Care was the top prolific journal. Antiretroviral therapy and adherence, men has sex with men, mental health, substance abuse, stigma, and Sub-Saharan Africa were the central topics regarding the depression-related research in HIV/AIDS. Conclusion This bibliometric analysis reported the publication trend, major contributing countries/regions, institutions, authors, journals and mapped the knowledge network of depression-related research on HIV/AIDS. In this field, topics such as “adherence,” “mental health,” “substance abuse,” “stigma,” “men who have sex with men” and “South Africa” have attracted considerable attention.