Background: The challenges faced by the Global South during the coronavirus disease (COVID-19) pandemic are compounded by the presence of informal settlements, which are typically densely populated and lacking in formalized sanitation infrastructure. Social distancing measures in informal settlements may be difficult to implement due to the density and layout of settlements. This study measures the distance between dwellings in informal settlements in Cape Town to identify the risk of COVID-19 transmission. Objective: The aim of this paper is to determine if social distancing measures are achievable in informal settlements in Cape Town, using two settlements as an example. We will first examine the distance between dwellings and their first, second, and third nearest neighbors and then identify clusters of dwellings in which residents would be unable to effectively practice social isolation due to the close proximity of their homes. Methods: Dwellings in the settlements of Masiphumelele and Klipfontein Glebe were extracted from a geographic information system data set of outlines of all informal dwellings in Cape Town. The distance to each dwelling's first, second, and third nearest neighbors was calculated for each settlement. A social distance measure of 2 m was used (buffer of 1 m, as dwellings less than 2 m apart are joined) to identify clusters of dwellings that are unable to effectively practice social distancing in each settlement. Results: The distance to each dwelling's first 3 nearest neighbors illustrates that the settlement of Masiphumelele is constructed in a denser fashion as compared to the Klipfontein Glebe settlement. This implies that implementing social distancing will likely be more challenging in Masiphumelele than in Klipfontein Glebe. However, using a 2-m social distancing measure, it was demonstrated that large portions of Klipfontein Glebe would also be unable to effectively implement social distancing. Conclusions: Effectively implementing social distancing may be a challenge in informal settlements due to their density. This paper uses dwelling outlines for informal settlements in the city of Cape Town to demonstrate that with a 2 m measure, effective social distancing will be challenging.