BACKGROUND: Since WHO declared the COVID-19 pandemic a Public Health Emergency of International Concern, more than 20 million cases have been reported, as of Aug 24, 2020. This study aimed to identify what the additional health-care costs of a strategic preparedness and response plan (SPRP) would be if current transmission levels are maintained in a status quo scenario, or under scenarios where transmission is increased or decreased by 50%. METHODS: The number of COVID-19 cases was projected for 73 low-income and middle-income countries for each of the three scenarios for both 4-week and 12-week timeframes, starting from June 26, 2020. An input-based approach was used to estimate the additional health-care costs associated with human resources, commodities, and capital inputs that would be accrued in implementing the SPRP. FINDINGS: The total cost estimate for the COVID-19 response in the status quo scenario was US$52.45 billion over 4 weeks, at $8.60 per capita. For the decreased or increased transmission scenarios, the totals were $33.08 billion and $61.92 billion, respectively. Costs would triple under the status quo and increased transmission scenarios at 12 weeks. The costs of the decreased transmission scenario over 12 weeks was equivalent to the cost of the status quo scenario at 4 weeks. By percentage of the overall cost, case management (54%), maintaining essential services (21%), rapid response and case investigation (14%), and infection prevention and control (9%) were the main cost drivers. INTERPRETATION: The sizeable costs of a COVID-19 response in the health sector will escalate, particularly if transmission increases. Instituting early and comprehensive measures to limit the further spread of the virus will conserve resources and sustain the response. FUNDING: WHO, and UK Foreign Commonwealth and Development Office.