
This is a list of the largest knownepidemics andpandemics caused by aninfectious disease in humans. Widespreadnon-communicable diseases such ascardiovascular disease andcancer are not included. An epidemic is the rapid spread ofdisease to a large number of people in a given population within a short period of time; inmeningococcal infections, anattack rate in excess of 15 cases per 100,000 people for two consecutive weeks is considered an epidemic.[1] Due to the long time spans, thefirst plague pandemic (6th century – 8th century) and thesecond plague pandemic (14th century – early 19th century) are shown by individual outbreaks, such as thePlague of Justinian (first pandemic) and theBlack Death (second pandemic).
Infectious diseases with high prevalence are listed separately (sometimes in addition to their epidemics), such asmalaria, which may have killed 50–60 million people.[2]
Ongoing epidemics and pandemics are inboldface. 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, seeworld population.[3]
| Rank | Epidemics/pandemics | Disease | Death toll | Percentage of population lost | Years | Location |
|---|---|---|---|---|---|---|
| 1 | Plague of Justinian | Bubonic plague | 15–100 million | 25–60% of European population[4] | 541–549 | North Africa, Europe, and Western Asia |
| 2 | HIV/AIDS pandemic | HIV/AIDS | 44 million (as of 2025[update]) | – | 1981–present[5] | Worldwide |
| 3 | Black Death | Bubonic plague | 25–50 million | 30–60% of European population[6] | 1346–1353 | Europe, Asia, and North Africa |
| 4 | 1918 "Spanish" influenza pandemic | Influenza A/H1N1 | 25-50 million | 1–5.4% of global population[7] | 1918–1920 | Worldwide |
| 5 | COVID-19 pandemic | COVID-19 | 7.1-36.5 million[8][9](as of 2025) | – | 2019[a]–present[10][11][b] | Worldwide |
| 6 | Third plague pandemic | Bubonic plague | 12–15 million | – | 1855–1960 | Worldwide |
| 7 | Cocoliztli epidemic of 1545–1548 | Cocoliztli, caused by an unidentified pathogen | 5–15 million | 27–80% of Mexican population[12] | 1545–1548 | Mexico |
| 8 | Antonine Plague | Smallpox ormeasles | 5–10 million | 25–33% of Roman population[13] | 165–180 (possibly up to 190) | Roman Empire |
| 9 | 1520 Mexico smallpox epidemic | Smallpox | 5–8 million | 23–37% of Mexican population[12] | 1519–1520 | Mexico |
| 10 | 1957–1958 influenza pandemic | Influenza A/H2N2 | 1–4 million | – | 1957–1958 | Worldwide |
| 11 | Hong Kong flu | Influenza A/H3N2 | 1–4 million | – | 1968–1969 | Worldwide |
| 12 | 1918–1922 Russia typhus epidemic | Typhus | 2–3 million | 1–1.6% of Russian population[14] | 1918–1922 | Russia |
| 13 | Cocoliztli epidemic of 1576 | Cocoliztli | 2–2.5 million | 50% of Mexican population[12] | 1576–1580 | Mexico |
| 14 | 1772–1773 Persian Plague | Bubonic plague | 2 million | – | 1772–1773 | Persia |
| 15 | 735–737 Japanese smallpox epidemic | Smallpox | 2 million | 33% of Japanese population[15] | 735–737 | Japan |
| 16 | Naples Plague | Bubonic plague | 1.25 million | – | 1656–1658 | Southern Italy |
| 17 | 1889–1890 pandemic | Influenza orhuman coronavirus OC43[16][17] | 1 million | – | 1889–1890 | Worldwide |
| 18 | 1629–1631 Italian plague | Bubonic plague | 1 million | – | 1629–1631 | Italy |
| 19 | 1846–1860 cholera pandemic | Cholera | 1 million | – | 1846–1860 | 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 ofCanaan | Amarna letters EA 244,Biridiya, the mayor of Megiddo complains toAmenhotep III of his area being "consumed by death, plague and dust" | Unknown | [29] |
| Hittite Plague/"Hand of Nergal" | 1330 BC (circa) | Near East,Hittite Empire,Alashiya, possiblyEgypt | Unknown, possiblyTularemia. Mentioned inAmarna letter EA 35 as the "Hand of Nergal", cause of death ofŠuppiluliuma I. | Unknown | |
| Plague of Athens | 430–426 BC | Greece,Libya, Egypt,Ethiopia | Unknown, possiblytyphus,typhoid fever orviral hemorrhagic fever | 75,000–100,000 | [30][31][32][33] |
| 412 BC epidemic | 412 BC | Greece (Northern Greece,Roman Republic) | Unknown, possiblyinfluenza | 473,000 (10% of the Roman Population) | [34] |
| Antonine Plague | 165–180 (possibly up to 190) | Roman Empire | Unknown, possiblysmallpox | 5–10 million | [35][36] |
| Jian'an Plague | 217 | Han dynasty | Unknown, possiblytyphoid fever orviral hemorrhagic fever | 2 million | [37][38] |
| Plague of Cyprian | 249–262 | Europe | Unknown, possiblysmallpox | 310,000 | [39][40] |
| Plague of Justinian (beginning offirst plague pandemic) | 541–549 | Europe andWest Asia | Bubonic plague | 15–100 million | [4][41][42] |
| 580 Dysentery Epidemic in Gaul | 580 | Gaul | Dysentery or possibly smallpox | 450,000 (10% of theGaul population) | [43] |
| Roman Plague of 590 (part offirst plague pandemic) | 590 | Rome,Byzantine Empire | Bubonic plague | Unknown | [44] |
| Plague of Sheroe (part offirst plague pandemic) | 627–628 | Bilad al-Sham | Bubonic plague | 25,000+ | |
| Plague of Amwas (part offirst plague pandemic) | 638–639 | Byzantine Empire,West Asia, Africa | Bubonic plague | 25,000+ | [45] |
| Plague of 664 (part offirst plague pandemic) | 664–689 | British Isles | Bubonic plague | Unknown | [46] |
| Plague of 698–701 (part offirst plague pandemic) | 698–701 | Byzantine Empire,West Asia,Syria,Mesopotamia | Bubonic plague | Unknown | [47] |
| 735–737 Japanese smallpox epidemic | 735–737 | Japan | Smallpox | 2 million (approx.1⁄3 of Japanese population) | [15][48] |
| Plague of 746–747 (part offirst plague pandemic) | 746–747 | Byzantine Empire,West Asia, Africa | Bubonic plague | Unknown | [45] |
| Black Death (start of thesecond plague pandemic) | 1346–1353 | Eurasia andNorth Africa | Bubonic plague | 75–200 million (30–60% of European population and 33% percent of the Middle Eastern population) | [49] |
| Sweating sickness (multiple outbreaks) | 1485–1551 | Britain (England) and later continental Europe | Unknown, possibly an unknown species ofhantavirus | 10,000+ | [50] |
| 1489 Spain typhus epidemic | 1489 | Spain | Typhus | 17,000 | [51] |
| Event | Years | Location | Disease | Death toll (estimate) | Ref. |
|---|---|---|---|---|---|
| Seventh cholera pandemic | 1961–present | Worldwide | Cholera (El Tor strain) | 36,000[citation needed] | [323] |
| HIV/AIDS pandemic | 1981–present | Worldwide | HIV/AIDS | 44 million (as of 2025[update]) | [324] |
| MERS outbreak | 2012–present | Worldwide | Middle East respiratory syndrome / MERS-CoV | 941 (as of 8 May 2021[update]) | [325][326] |
| COVID-19 pandemic | 2019[a]–present | Worldwide | COVID-19 | 7.1–36.5 million | [328] |
| 2023–2025 mpox epidemic | 2023–present | Worldwide, primarily Africa | Mpox | 812 | [329] |
| 2024–2025 Sudanese cholera epidemic | 2024–present | Sudan,South Sudan, andChad | Cholera | 5,869 | [330] |
spain 1788 dengue fever.