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Background: Currently, 410,000 new HIV infections among youth occur worldwide, which is a significant public health issue. Members of the clergy can be trustworthy allies in the reduction of HIV infections among the youth. However, little is known regarding their knowledge as well as the perceptions they hold towards HIV prevention among young people. Thus, we explored the knowledge and perceptions of religious leaders regarding HIV prevention among young people (15-24 years) in Lira district., Methods: This was a cross-sectional qualitative study conducted among 20 religious leaders in March 2021 in Lira district. Religious leaders were sampled purposively and recruited from modern religions (beliefs influenced by Christianity or Islam) in Lira district. Guides for key informant interviews were utilized to gather information. Each interview was audio recorded, transcribed, and entered into NVivo version 12 software, and the data was then ready for analysis. The main themes were determined using thematic analysis., Results: Although a few individuals had some misconceptions, the majority of participants had good knowledge about the transmission and prevention of HIV. Participants knew awareness creation, abstinence, and faithfulness in marriage as HIV prevention strategies and held positive perceptions. Perceived barriers to HIV prevention involvement were lack of knowledge and training, and inadequate resources whereas motivating factors were; being respected, and trusted, and having easy access to young people., Conclusion: In conclusion, religious leaders show limited HIV prevention knowledge due to religious beliefs, but understand the importance of measures like abstinence. Despite challenges, their involvement is crucial. Addressing knowledge gaps and providing support is vital. Future efforts should emphasize both behavioral measures and interventions like condom use, Post Exposure Prophylaxis, and Pre-Exposure Prophylaxis., Competing Interests: Competing interests Authors have no competing interests.