Background Although COVID-19 outcomes vary between and within countries, there is little published data on how aspects of social determinants of health (SDoH) affect COVID-19 outcomes in the African context. Objective The current study set to examine COVID-19 case and death rates and their correlates among African countries using data from different sources. Methods An ecological cross-sectional study comprising 28 African countries with a recent Demographic and Health Survey, DHS (2010-2018). Response variables were COVID-19 case and death rates (as of August 15, 2020). Covariates comprised three healthcare systems measures; rates of hospital beds (2005-2017), ventilators (2020) and doctors (2010-2018) per 10,000 population, and 9 broad topics common to multiple SDoH frameworks aggregated to the country level; geography (urban residence), wealth index, education, employment, crowding, and access to information. Rates per 10,000 population were calculated for healthcare measures and mapped for visualization. A Negative Binomial regression was used to assess whether aspects of SDoH are correlated with COVID-19. Results Our analysis indicated that 1 in 4 (25.1%) households in study countries are without clean water and handwashing access. Country-level health system capacity (hospital beds, ventilators, and medical doctors) varied considerably between the countries. Negative Binomial regression showed that the odds of COVID-19 morbidity and death was higher in countries with a high proportion of households without access to quality water and doctors per 10,000 people. Having a high proportional of educated women (1.003: 95% CI, 1.001 – 1.005), hospital beds per population and less people per room (0.959: 95% CI, 0.920 – 1.000) was negatively correlated with COVID-19 deaths while being insured and owning a mobile phone was correlated with illness. Conclusion Both aspects of SDoH and healthcare system contribute either negatively or positively to COVID-19 outcomes. Addressing healthcare system capacity and economic and environmental SDoH will be critical for mitigating the spread of COVID-19 and re-emerging diseases on the African continent.