The fisheries sector contributes significantly to Malawi's national economy and to the livelihoods of the poor as certain activities in the sector have relatively low barriers to entry. Various studies have shown that the fisheries sector suffers from high HIV prevalence in many low-income countries. In Malawi, HIV prevalence as well as the causes and impact of HIV infections among fisherfolk are yet to be assessed. Participatory action research was conducted in Mangochi District, in the southern part of Lake Malawi, between December 2007 and January 2008, to identify critical HIV-risk points along the value-chain for the Lake Sardine or usipa (Engraulicypris sardella) fishery. Data were collected through interviews with key informants and from focus group discussions at the community, institution, district and market levels. An analysis of vulnerability resulted in the formulation of mechanisms to redress HIV and AIDS prevention and mitigation at each point of vulnerability. The findings show that HIV and AIDS vulnerability in the fishery's market-chain is highest where fish processing and trading influence sexual relationships between fishermen and female fish traders. The period of high usipa catches (December to March) coincides with a period of food shortage and fishing offers income-generating opportunities for many food-insecure households. This increases competition in processing and trading fish, a socio-economic situation that may result in increased instances of transactional sex. The interactions along the usipa fishery's market-chain, from rural to urban settings, also favour the transmission of HIV from areas of high prevalence to areas with otherwise low HIV risk.