In West African countries, borders create opportunities for informal networks of trade and exchange. Some of the women involved in activities across the borders operate without official permit. Thus, they engage in transactional sex with those who may facilitate their movement across borders. The study examines sexual relations in cross-border trade and their implications for HIV spread in Nigeria. The study was carried out at Seme, a border town between Lagos, Nigeria, and Republic of Benin. The qualitative method was used to collect data for the study. Forty women who were cross-border traders were selected for focus group discussions; they were stratified into four sessions based on the type of goods, age, and years of experience. In-depth interviews (IDIs) were used to elicit information from three drivers and 16 security agents. The study revealed that some of these women used sex as a means of negotiation with border officials to avoid their goods being confiscated, whereas others had extramarital affairs with some of the officials for financial gains and protection. None of the women interviewed used condom during her last sexual intercourse preceding the survey. More than two-thirds of the respondents had heard about HIV/AIDS, but believed that they were not at risk of infection due to their ignorance. The study concluded that the observed sexual relationships may act as conduit for HIV and sexually transmitted infections (STIs) into both Nigeria and Benin, as these create sexual networks that may stretch over a wide geographical area. There is a need for mobile education programs targeted at this high-risk group.