Purpose: In May, 2020, one of the authors (GM) reported a profound initial disparity in COVID mortality rates between developed western nations (DWN) and countries in malaria-endemic regions. We sought to confirm and understand this disparity. Methods: We performed a comparative analysis of COVID-19 (hereinafter COVID) fatality rates from March 1, 2020, until July 1, 2021. We compared six sub-Saharan African countries (SSA), fn1 selected for their high rates of malaria (Nigeria, DR Congo, Uganda, Mozambique, Côte d’Ivoire, and Niger), to four DWNs with essentially no malaria. Raw mortality data was obtained from Our World in Data. The end-of-month numbers were cross checked for accuracy. We searched the scientific literature to determine uses and roles of antimalarial drugs in the COVID pandemic and the individual antimalarial agents used in these SSA countries. Results: People living in the DWN died from COVID at a rate approximately 120 times that of people in the SSA group. When corrected for differences in age distribution, the DWN fatality rates were approximately twenty times those of SSA. This profound disparity persisted over the study period. There is a strong correlation between a country’s use of antimalarial drugs and low COVID death rates. Two antimalarial drugs, with reported anti-SARS-CoV-2 activity, artemisinin and the atovaquone-proguanil combination (AV-PG), were in widespread use in SSA. No antimalarial was in widespread use in the DWN. Hydroxychloroquine has a limited role in the treatment of autoimmune disease in DWN, but its use was largely prohibited for COVID treatment. Conclusion : The profoundly lower mortality rates for people living in SSA versus the DWN appears to be explained by widespread use of antimalarial drugs which have unanticipated crossover efficacy against SARS-CoV-2 as well. The two most likely drugs are artemisinin and AV-PG. Such anti-COVID crossover effects of antimalarial drugs have been largely overlooked/ignored by those with health policy authority in DWN. Such crossover efficacy deserves urgent and thorough examination.