This article needs to be updated. (June 2026) |
Infectious diseases with high prevalence are separately (sometimes in addition to their epidemics), such as malaria, which may have killed 50–60 million people.
Ongoing epidemics and pandemics are in bold face. For a given epidemic or pandemic, the average of its estimated death toll range is used for ranking. If the death toll averages of two or more epidemics or pandemics are equal, then the smaller the range, the higher the rank. For the historical records of major changes in the world population, see world population.
| Rank | Epidemics/pandemics | Disease | Death toll (million) | Percentage of population lost | Years | Location |
|---|---|---|---|---|---|---|
| 1 | 1918 "Spanish" influenza pandemic | Influenza A/H1N1 | 25–100 | 1–5.4% of global population | 1918–1920 | Worldwide |
| 2 | Plague of Justinian | Bubonic plague | 15–100 | 25–60% of European population | 541–549 | North Africa, Europe, and Western Asia |
| 3 | HIV/AIDS pandemic | HIV/AIDS | 45 (as of 2026[update]) | ? | 1981–present | Worldwide |
| 4 | Black Death | Bubonic plague | 25–50 | 30–60% of European population | 1346–1353 | North Africa, Europe, and Asia |
| 5 | COVID-19 pandemic | COVID-19 | 7.12–38 (as of 2026) | 0.4375% of global population (as of 2026) | 2019–present | Worldwide |
| 6 | Third plague pandemic | Bubonic plague | 12–15 | ? | 1855–1960 | Worldwide |
| 7 | Cocoliztli epidemic of 1545–1548 | Cocoliztli (caused by an unidentified pathogen) | 5–15 | 27–80% of Mexican population | 1545–1548 | Mexico |
| 8 | Antonine Plague | Smallpox or measles | 5–10 | 25–33% of Roman population | 165–180 (possibly up to 190) | Roman Empire |
| 9 | 1520 Mexico smallpox epidemic | Smallpox | 5–8 | 23–37% of Mexican population | 1519–1520 | Mexico |
| 10 | Seventh cholera pandemic | Cholera | 1.4–9.3 (as of 2026) | ? | 1961–present | Worldwide |
| 11 | 1957–1958 influenza pandemic | Influenza A/H2N2 | 1–4 | ? | 1957–1958 | Worldwide |
| 12 | Hong Kong flu | Influenza A/H3N2 | 1–4 | ? | 1968–1969 | Worldwide |
| 13 | 1918–1922 Russia typhus epidemic | Typhus | 2–3 | 1–1.6% of Russian population | 1918–1922 | Russia |
| 14 | Cocoliztli epidemic of 1576 | Cocoliztli | 2–2.5 | 50% of Mexican population | 1576–1580 | Mexico |
| 15 | Jian'an Plague | Unknown (possibly typhoid fever or viral hemorrhagic fever) | 2 | ? | 217 | Han dynasty |
| 16 | 735–737 Japanese smallpox epidemic | Smallpox | 2 | 33% of Japanese population | 735–737 | Japan |
| 17 | 1772–1773 Persian Plague | Bubonic plague | 2 | ? | 1772–1773 | Persia |
| 18 | Naples Plague | Bubonic plague | 1.25 | ? | 1656–1658 | Italy (Southern) |
| 19 | 1629–1631 Italian plague | Bubonic plague | 1 | ? | 1629–1631 | Italy |
| 20 | 1846–1860 cholera pandemic | Cholera | 1 | ? | 1846–1860 | Worldwide |
| 21 | 1889–1890 pandemic | Influenza or human coronavirus OC43 | 1 | ? | 1889–1890 | Worldwide |
There have been various major infectious diseases with high prevalence worldwide, but they are currently not listed in the above table as epidemics/pandemics due to the lack of definite data, such as time span and death toll.

| Event | Years | Location | Disease | Death toll (estimate) | Ref. |
|---|---|---|---|---|---|
| 1350 BC plague of Megiddo | 1350 BC (circa) | Megiddo, land of Canaan | Unknown. In the Amarna letters EA 244, Biridiya, the mayor of Megiddo complains to Amenhotep III of his area being "consumed by death, plague and dust" | ? | |
| Hittite Plague/"Hand of Nergal" | 1330 BC (circa) | Near East, Hittite Empire, Alashiya, possibly Egypt | Unknown, possibly Tularemia. Mentioned in Amarna letter EA 35 as the "Hand of Nergal", cause of death of Šuppiluliuma I. | ? | |
| Plague of Athens | 430–426 BC | Greece, Libya, Egypt, Ethiopia | Unknown, possibly typhus, typhoid fever or viral hemorrhagic fever | 75,000–100,000 | |
| 412 BC epidemic | 412 BC | Greece (Northern Greece, Roman Republic) | Unknown, possibly influenza | 473,000 (10% of the Roman Population) | |
| Antonine Plague | 165–180 (possibly up to 190) | Roman Empire | Unknown, possibly smallpox | 5–10 million | |
| Jian'an Plague | 217 | Han dynasty | Unknown, possibly typhoid fever or viral hemorrhagic fever | 2 million | |
| Plague of Cyprian | 249–262 | Europe | Unknown, possibly smallpox or viral hemorrhagic fever | 310,000 | |
| Plague of Justinian (beginning of first plague pandemic) | 541–549 | Europe and West Asia | Bubonic plague | 15–100 million | |
| 580 Dysentery Epidemic in Gaul | 580 | Gaul | Dysentery or possibly smallpox | 450,000 (10% of the Gaul population) | |
| Roman Plague of 590 (part of first plague pandemic) | 590 | Rome, Byzantine Empire | Bubonic plague | ? | |
| Plague of Sheroe (part of first plague pandemic) | 627–628 | Bilad al-Sham | Bubonic plague | 25,000+ | |
| Plague of Amwas (part of first plague pandemic) | 638–639 | Byzantine Empire, West Asia, Africa | Bubonic plague | 25,000+ | |
| Plague of 664 (part of first plague pandemic) | 664–689 | British Isles | Bubonic plague | ? | |
| Plague of 698–701 (part of first plague pandemic) | 698–701 | Byzantine Empire, West Asia, Syria, Mesopotamia | Bubonic plague | ? | |
| 735–737 Japanese smallpox epidemic | 735–737 | Japan | Smallpox | 2 million (approx. 1⁄3 of Japanese population) | |
| Plague of 746–747 (part of first plague pandemic) | 746–747 | Byzantine Empire, West Asia, Africa | Bubonic plague | ? | |
| Black Death (start of the second plague pandemic) | 1346–1353 | Eurasia and North Africa | Bubonic plague | 25–50 million (30–60% of European population and 33% percent of the Middle Eastern population) | |
| Sweating sickness (multiple outbreaks) | 1485–1551 | Britain (England) and later continental Europe | Unknown, possibly an unknown species of hantavirus | 10,000+ | |
| 1489 Spain typhus epidemic | 1489 | Spain | Typhus | 17,000 | |
| Event | Years | Location | Disease | Death toll (estimate) | Ref. |
|---|---|---|---|---|---|
| 1510 influenza pandemic | 1510 | Asia, North Africa, Europe | Influenza | Unknown, around 1% of those infected | |
| 1520 Mexico smallpox epidemic | 1519–1520 | Mexico | Smallpox | 5–8 million (40% of population) | |
| Cocoliztli epidemic of 1545–1548 | 1545–1548 | Mexico | Possibly Salmonella enterica | 5–15 million (80% of population) | |
| 1557 influenza pandemic | 1557–1559 | Asia, Africa, Europe, and Americas | Influenza | Unknown (10% of the infected) | |
| 1561 Chile smallpox epidemic | 1561–1562 | Chile | Smallpox | 120,000–150,000 (20–25% of native population) | |
| 1563 London plague (part of the second plague pandemic) | 1563–1564 | London, England | Bubonic plague | 20,100+ | |
| Cocoliztli epidemic of 1576 | 1576–1580 | Mexico | Possibly Salmonella enterica | 2–2.5 million (50% of population) | |
| 1582 Tenerife plague epidemic (part of the second plague pandemic) | 1582–1583 | Tenerife, Spain | Bubonic plague | 5,000–9,000 | |
| 1592–1596 Seneca nation measles epidemic | 1592–1596 | Seneca nation, North America | Measles | ? | |
| 1592–1593 Malta plague epidemic (part of the second plague pandemic) | 1592–1593 | Malta | Bubonic plague | 3,000 | |
| 1592–1593 London plague (part of the second plague pandemic) | 1592–1593 | London, England | Bubonic plague | 19,900+ | |
| 1596–1602 Spain plague epidemic (part of the second plague pandemic) | 1596–1602 | Spain | Bubonic plague | 600,000–700,000 | |
| Event | Years | Location | Disease | Death toll (estimate) | Ref. |
|---|---|---|---|---|---|
| Seventh cholera pandemic | 1961–present | Worldwide | Cholera (El Tor strain) | 1.4-9.3 million; 21,000–143,000 each year (as of 2026) | |
| HIV/AIDS pandemic | 1981–present | Worldwide | HIV/AIDS | 45 million (as of 2026[update]) | |
| MERS outbreak | 2012–present | Worldwide | Middle East respiratory syndrome / MERS-CoV | 959 (as of 30 March 2026[update]) | |
| COVID-19 pandemic | 2019–present | Worldwide | COVID-19 | 7.12–38 million (as of 2026) | |
| 2023–2026 mpox epidemic | 2023–present | Worldwide, primarily Africa | Mpox | 812 | |
| 2024–2026 Sudanese cholera epidemic | 2024–present | Sudan, South Sudan, and Chad | Cholera | 3573 | |
| 2026 Bangladesh measles outbreak | 2026–present | Bangladesh | Measles | 1,233 | |
| 2026 Ebola epidemic | 2026–present | Democratic Republic of the Congo, Uganda, Kenya | Ebola | 4,964 | |
| 2026 United States cyclosporiasis outbreak | 2026 | United States | Cyclosporiasis | 2 | |
spain 1788 dengue fever.