BACKGROUND: Following success demonstrated with the HIV Self-Testing AfRica Initiative, HIV self-testing (HIVST) is being added to national HIV testing strategies in Southern Africa. An analysis of the costs of scaling up HIVST is needed to inform national plans, but there is a dearth of evidence on methods for forecasting costs at scale from pilot projects. Econometric cost functions (ECFs) apply statistical inference to predict costs; however, we often do not have the luxury of collecting large amounts of location-specific data. We fit an ECF to identify key drivers of costs, then use a simpler model to guide cost projections at scale. METHODS: We estimated the full economic costs of community-based HIVST distribution in 92 locales across Malawi, Zambia, Zimbabwe, South Africa and Lesotho between June 2016 and June 2019. We fitted a cost function with determinants related to scale, locales organisational and environmental characteristics, target populations, and per capita Growth Domestic Product (GDP). We used models differing in data intensity to predict costs at scale. We compared predicted estimates with scale-up costs in Lesotho observed over a 2-year period. RESULTS: The scale of distribution, type of community-based intervention, percentage of kits distributed to men, distance from implementer's warehouse and per capita GDP predicted average costs per HIVST kit distributed. Our model simplification approach showed that a parsimonious model could predict costs without losing accuracy. Overall, ECF showed a good predictive capacity, that is, forecast costs were close to observed costs. However, at larger scale, variations of programme efficiency over time (number of kits distributed per agent monthly) could potentially influence cost predictions. DISCUSSION: Our empirical cost function can inform community-based HIVST scale-up in Southern African countries. Our findings suggest that a parsimonious ECF can be used to forecast costs at scale in the context of financial planning and budgeting.