Phase I and II HIV vaccine trials are currently underway in South Africa. Sites are being prepared for Phase III vaccine trials. Participants in these trials risk exposure to 'social harms' that may impact on participant enrolment and retention and threaten their welfare. Potential social harms should be prevented, minimised and/or addressed. This paper examines the literature on potential social harms in HIV vaccine trials. It outlines the type and severity and frequency of potential social harms and ways these have been monitored in settings in the developed world and Thailand. We argue that many of these social harms are likely to manifest in South African trials, however, it is also likely social harms may manifest differently in our setting, such as domestic violence. Therefore careful formative research is required to identify what constitutes a social harm in our setting. Measures should be carefully tailored to record such events and methods established to prevent or address these.