The transport sector plays a major role in Southern Africa's social and economic development. Globally the region is regarded as the most HIV/AIDS prevalent region making its impact of major concern. Applying qualitative methodologies involving extensive literature review and analysis, and complemented by some primary data gathering, the study assessed the relationship between the transport sector and HIV/AIDS in Southern Africa. This study established that transport sectors are more exposed to HIV/AIDS as a result of the nature of their working conditions. Furthermore, it was established that the transport sector, through facilitating mobility, plays a bigger role in the general spread of HIV/AIDS. The study recommends sector specifically tailored HIV/AIDS reduction plans and strategies that integrate all stakeholders if the scourge of HIV/AIDS is to be curtailed.