Background Coronavirus disease (COVID-19) continues to ravage both the health and economy of South Africa. This study estimated the total present value of human life (TPVHL) losses associated with COVID-19 in South Africa. Methods The human capital approach (HCA) was used to value the 101,146 human life losses associated with COVID-19 in South Africa as of 30 May 2022 – assuming South Africa’s average life expectancy of 64.88 years and a 3% discount rate. The TPVHL was the sum of discounted values of human life (VHL) across the 17 age groups. The PVHL for each age group is the product of the sum of discounted years of life lost per person, gross domestic product per capita net of current health expenditure per person, and the number of COVID-19 deaths borne by a specific age group. During sensitivity analysis, the HCA model was reanalysed four times alternately, assuming a 5% discount rate, 10% discount rate, Africa’s highest average life expectancy of 78.76 years (Algeria females), and the world’s highest life expectancy of 88.17 years (Hong Kong females). Results The 101,146 human lives lost had a TPVHL of Int$7,566,656,063, and an average of Int$74,809 per human life lost to COVID-19. Subsequent re-calculation of the model with a 5% and 10% discount rates diminished the TPVHL by Int$1,177,446,403 (15.6%) and Int$2,997,459,371 (39.6%), respectively. Further, a reanalysis of the model with Africa’s highest average life expectancy and the world’s highest life expectancy triggered growth in the TPVHL of Int$8,846,142,813 (116.9%) and Int$15,363,165,669 (203.04%), respectively. Conclusions The average discounted value per human life lost to COVID-19 of Int$74,809 is five-fold the GDP per capita for South Africa in 2022, setting the country back a few years in terms of socio-economic development. Thus, COVID-19 continues to have a significant negative impact on the life and livelihoods of South Africans. The economic evidence complements the human rights case for increased domestic investment into health-related systems to bridge the gaps in coverage of health development-related services.