ABSTRACT: As with other countries globally, Rwanda has faced a recent outbreak of the coronavirus disease 2019 (COVID-19) against a backdrop of an HIV epidemic. At present, there is no successful cure or vaccine for both COVID-19 and HIV. People with underlying conditions, including HIV, are at increased risk of severe COVID-19 manifestations. This underscores the need to enhance the knowledge, attitudes, and practice of people living with HIV (PLWH) to protect this population against COVID-19. An institution-based cross-sectional study was conducted from August 31 to September 18, 2020 among 376 participants who were selected by a simple random sampling technique. A pretested and structured self-administered questionnaire was used to collect data. Quality scores were calculated as a measure of the participants' knowledge, attitudes, and practice (KAP) levels. The student t-test was used to compare continuous variables between low (<65%) and high (?65%) KAP scores. The chi-square test was used to determine the association between KAP scores and categorical variables. All decisions on statistical tests were concluded at 5% level of significance. All statistical analysis was performed using STATA statistical package version 11.2 (STATA Corp., Texas, USA). Of the 376 participants, 363 (97%) obtained a high knowledge score, while more than a quarter of the participants (26%) had a poor attitude score, and the majority (90%) having a high practice score. There was no association between gender, age, place of residence, employment, or duration on ART and knowledge score. Employment status and duration on antiretroviral treatment (ART) were significantly associated with attitude scores (p?=?0.004 and p?=?0.013, respectively). Gender and duration on ART were significantly associated with practice scores (p?=?0.02 and p?=?0.012, respectively). There was a moderate positive correlation (r?=?0.57) between knowledge and attitude scores, and knowledge and practice scores (r?=?0.55). There was a strong positive correlation (r?=?0.67) between attitude scores and practice scores. Health education programs tailored for PLWH and aimed at mobilizing and improving COVID-19-related knowledge, attitude, and practice should be prioritized in the Rwandan COVID-19 response.