HISTORY

Disease

Deadliest Disease Outbreaks by Death Toll

This list features the deadliest pandemics in history based on death toll.

RANK	PANDEMIC	DISEASE	DEATH TOLL	YEARS	LOCATION
1	Black Death	Bubonic plague	75-200 million	1346–1353	Europe; Asia; North Africa
2	Spanish flu	Influenza A/H1N1	50 million	1918–1920	Worldwide
3	Plague of Justinian	Bubonic plague	30-50 million	541–549	North Africa; Europe; Western Asia
4	HIV/AIDS pandemic	HIV/AIDS	42.3 million	1981–present	Worldwide
5	Cocoliztli epidemic of 1545–1548	Cocoliztli, caused by an unidentified pathogen	5–15 million	1545–1548	Mexico
6	Third plague pandemic	Bubonic plague	12 million	1855–1960	Worldwide
7	Antonine Plague	Smallpox or measles	5–10 million	165–180/190	Roman Empire
8	1520 Mexico smallpox epidemic	Smallpox	5–8 million	1519–1520	Mexico
9	COVID-19 pandemic	COVID-19	7 million	2019–present	Worldwide
10	1918–1922 Russia typhus epidemic	Typhus	3 million	1918–1922	Russia
11	Cocoliztli epidemic of 1576	Cocoliztli	2–2.5 million	1576–1580	Mexico
12	735–737 Japanese smallpox epidemic	Smallpox	1.5-2 million	735–737	Japan
13	1772–1773 Persian Plague	Bubonic plague	2 million	1772–1773	Persia
14	Naples Plague	Bubonic plague	1.25 million	1656–1658	Southern Italy
15	1957–1958 influenza pandemic	Influenza A/H2N2	1.1 million	1957–1958	Worldwide

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References

Pires, A., et al. (2022) ‘Epidemiological characteristics of the 1957–1958 influenza pandemic’, ScienceDirect. Available at: https://www.sciencedirect.com/science/article/pii/S0755498222000045 (Accessed 1 December 2025). Time Graphics (2023) Pandemics timeline. Available at: https://time.graphics/period/2981465 (Accessed 1 December 2025). DBpedia (2023) 1846–1860 cholera pandemic. Available at: https://dbpedia.org/page/1846–1860_cholera_pandemic (Accessed 1 December 2025). CDC (2012) ‘Emerging Infectious Diseases’, CDC EID. Available at: https://wwwnc.cdc.gov/eid/article/18/1/11-0597_article (Accessed 1 December 2025). Paltiel, A. D., Zheng, A. and Zheng, A. (2016) ‘The impact of the COVID-19 pandemic on healthcare services’, NCBI. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037359/ (Accessed 1 December 2025). Simple Wikipedia (2023) 735–737 Japanese smallpox epidemic. Available at: https://simple.wikipedia.org/wiki/735–737_Japanese_smallpox_epidemic (Accessed 1 December 2025). Noymer, A. (2008) ‘The cocoliztli epidemic in 1576’, NCBI. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730237/ (Accessed 1 December 2025). CDC (2008) ‘1957-1958 pandemic influenza’, CDC Archives. Available at: https://archive.cdc.gov/www_cdc_gov/flu/pandemic-resources/1957-1958-pandemic.html (Accessed 1 December 2025). Worldometers (2024) COVID-19 coronavirus pandemic. Available at: https://www.worldometers.info/coronavirus/ (Accessed 1 December 2025). Kumc.edu (2023) ‘Typhus on the Eastern Front’, University of Kansas Medical Center. Available at: https://www.kumc.edu/school-of-medicine/academics/departments/history-and-philosophy-of-medicine/archives/wwi/essays/medicine/typhus-on-the-eastern-front.html (Accessed 1 December 2025). Noymer, A. (2008) ‘Cocoliztli epidemic impact on the native population’, NCBI. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730237/ (Accessed 1 December 2025). HistoryExtra (2023) ‘The Antonine Plague: Symptoms, Causes, and Impact’. Available at: https://www.historyextra.com/period/roman/antonine-plague-symptoms-cause-impact/ (Accessed 1 December 2025). GAVI (2023) History's seven deadliest plagues. Available at: https://www.gavi.org/vaccineswork/historys-seven-deadliest-plagues (Accessed 1 December 2025). Noymer, A. (2008) ‘Cocoliztli epidemic from 1545’, NCBI. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730237/ (Accessed 1 December 2025). WHO (2023) Data on the size of the HIV/AIDS epidemic. Available at: https://www.who.int/data/gho/data/themes/topics/topic-details/GHO/data-on-the-size-of-the-hiv-aids-epidemic (Accessed 1 December 2025). Bell, R. (2023) ‘The impact of the Black Death’, American Scientist. Available at: https://www.americanscientist.org/article/the-bright-side-of-the-black-death (Accessed 1 December 2025). National Geographic (2023) ‘The Justinian Plague: Black Death Bacteria’, National Geographic. Available at: https://www.nationalgeographic.com/animals/article/140129-justinian-plague-black-death-bacteria-bubonic-pandemic (Accessed 1 December 2025). National Archives (2023) ‘The Influenza Epidemic’, National Archives. Available at: https://www.archives.gov/exhibits/influenza-epidemic/ (Accessed 1 December 2025). Wikipedia (2023) List of epidemics and pandemics. Available at: https://en.wikipedia.org/wiki/List_of_epidemics_and_pandemics#By_death_toll (Accessed 1 December 2025).

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