In Uganda, nurses do not always practice universal precautions unless they know the patients' HIV status. In our study, focused ethnography was used to explore the experiences of Ugandan nurses in the practice of universal precautions while caring for persons living with HIV. In-depth interviews were completed with 16 participants from a variety of units at a large teaching hospital in Uganda. Although participants were knowledgeable about universal precautions, the primary challenge to the practice of universal precautions was the inadequate supply of resources, both material and human. Despite challenges, the nurses displayed an enthusiasm for their work and a dedication to provide the best possible care for patients. The findings highlight the urgent need for governments and institutions, particularly in resource-constrained countries, to develop and implement policies related to universal precaution practice and to provide a consistent supply of protective equipment to ensure that universal precautions are consistently used.