Background South Africa recently experienced a first peak in COVID-19 cases and mortality. Dexamethasone and remdesivir both have the potential to reduce COVID-related mortality, but their cost-effectiveness in a resource-limited setting with scant intensive care resources is unknown. Methods We projected intensive care unit (ICU) needs and capacity from August 2020 to January 2021 using the South African National COVID-19 Epi Model. We assessed cost-effectiveness of 1) administration of dexamethasone to ventilated patients and remdesivir to non-ventilated patients, 2) dexamethasone alone to both non-ventilated and ventilated patients, 3) remdesivir to non-ventilated patients only, and 4) dexamethasone to ventilated patients only; all relative to a scenario of standard care. We estimated costs from the healthcare system perspective in 2020 USD, deaths averted, and the incremental cost effectiveness ratios of each scenario. Results Remdesivir for non-ventilated patients and dexamethasone for ventilated patients was estimated to result in 1,111 deaths averted (assuming a 0-30% efficacy of remdesivir) compared to standard care, and save $11.5 million. The result was driven by the efficacy of the drugs, and the reduction of ICU-time required for patients treated with remdesivir. The scenario of dexamethasone alone to ventilated and non-ventilated patients requires additional $159,000 and averts 1,146 deaths, resulting in $139 per death averted, relative to standard care. Conclusions The use of dexamethasone for ventilated and remdesivir for non-ventilated patients is likely to be cost-saving compared to standard care. Given the economic and health benefits of both drugs, efforts to ensure access to these medications is paramount.