Much of the research on behavioural preferences as predictors of compliance with regulations aimed at reducing the transmission of COVID-19 has focused on developed countries, with very little consideration of African countries. We conduct an online survey (n = 1503) considering beliefs, and individual and social preferences as predictors of compliance with prophylactic measures and lockdown regulations in South Africa. We use incentivized experimental measures of individual (risk and time) preferences and social preferences (cooperativeness and altruism). We also consider survey measures of risk tolerance, patience and trust. We find that beliefs about others’ behaviour are highly predictive of reported behaviour. We also find that greater patience and cooperativeness are predictive of high compliance with prophylactic measures and lockdown regulations. Encouragingly, respondents report higher compliance at higher lockdown levels, suggesting responsiveness of behaviour to the level of risk of infection.