South Africa reported it fist case of COVID-19 on 5 March 2020. While the first cases were imported, local transmission has led to a rapid increase in the number of cases. As of 21 April 2020, more than 3,400 cases and 58 deaths had been confirmed. On 15 March, President Cyril Ramaphosa declared a national state of disaster, and the government has since taken several measures to curb the spread of the virus, including closing borders, implementing strict social distancing measures and a 35-day nation-wide lockdown. These measures, along with the global economic shock caused by the pandemic, are expected to generate rising needs requiring an immediate and urgent response. Although South Africa is considered an upper-middle-income country, the amount of disparities—social, economic, and gender—make the country particularly vulnerable during this emergency. For example, 33 per cent of the urban population is concentrated in overcrowded slums; if the novel coronavirus is to strike this population, the probability of excess morbidity and mortality is a very real prospect. Furthermore, as a strategic regional business/socio-economic hub and key to the region’s socio-economic stability, a crisis in South Africa could have devastating broader regional consequences.