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1681 (MDCLXXXI) was a common year starting on Wednesday of the Gregorian calendar and a common year starting on Saturday (dominical letter B) of the Julian calendar, the 1681st year of the Common Era (CE) and Anno Domini (AD) designations, the 681st year of the 2nd millennium, the 81st year of the 17th century, and the 2nd year of the 1680s decade. As of the start of 1681, the Gregorian calendar was 10 days ahead of the Julian calendar, which remained in localized use until 1923.
- July 1 – Oliver Plunkett, Roman Catholic Archbishop of Armagh and Primate of All Ireland, falsely convicted in June of treason, is hanged, drawn and quartered at Tyburn, London, the last Catholic martyr to die in England; he is canonised in 1975.
- August – English sea captain Robert Knox of the East India Company escapes prison in Ceylon, and details his adventures across Kandy, and life in the kingdoms of the Tamil country Vanni, in his book An Historical Relation of the Island Ceylon.
- August 12 – Ahom King Gadadhar Singha (or Gadapani), who takes the Tai name Supaatphaa, ascends the throne.
- August 31 – English perjurer Titus Oates is told to leave his state apartments in Whitehall; his fame begins to wane, and he is soon arrested and imprisoned for sedition.
- September 30 – France annexes the city of Strasbourg (German: Strassburg), previously a free imperial city of the Holy Roman Empire.
- October 28 – A London woman is publicly flogged, for the crime of "involving herself in politics."
- December – Wu Shifan, grandson of Chinese general Wu Sangui, commits suicide in Yunnan province, ending the 8-year Revolt of the Three Feudatories against Qing Dynasty authority in China, at this time led by the Kangxi Emperor.
- December 22 – King Charles II of England signs a warrant for the building of the Royal Hospital Chelsea in London for wounded and retired soldiers.
- January 5 – Pietro Vidoni, Italian Catholic cardinal (b. 1610)
- January 27 – Edmund Bowyer, English politician (b. 1613)
- January 28 – Richard Allestree, English royalist churchman (b. c. 1621)
- March 6 – Michel de Marolles, French translator and churchman (b. 1600)
- March 12 – Frans van Mieris the Elder, Dutch painter (b. 1635)
- April 3 – Lucas Franchoys the Younger, Flemish painter (b. 1616)
- April 8 – Gabriel Druillettes, French missionary (b. 1610)
- April 10 – Philip I, Count of Schaumburg-Lippe (1640–1681) (b. 1601)
- April 11 – Frederick Louis, Count Palatine of Zweibrücken (b. 1619)
- April 12 – Pietro Paolini, Italian painter (b. 1603)
- April 26 – Charles Howard, 3rd Earl of Nottingham, son of Charles Howard (b. 1610)
- April 23 – Justus Sustermans, Flemish painter (b. 1597)
- May 4 – Johannes Musaeus, German theologian (b. 1613)
- May 6 – Sir Philip Wodehouse, 3rd Baronet, English baronet (b. 1608)
- May 24 – Nicodemus Tessin the Elder, Swedish architect (b. 1615)
- May 25 – Pedro Calderón de la Barca, Spanish dramatist and poet (b. 1600)
- June 9 – William Lilly, English astrologer (b. 1602)
- July 1 – Oliver Plunkett, Irish saint (b. 1629)
- July 8 – Georg Neumark, German poet and composer of hymns (b. 1621)
- July 10 – Christian Lupus, Flemish historian (b. 1612)
- July 20 – Louis Günther II, Count of Schwarzburg-Ebeleben (1642–1681) (b. 1621)
- July 25 – Urian Oakes, English-born President of Harvard University (b. 1631)
- August 12 – Sir George Wharton, 1st Baronet, English baronet (b. 1617)
- August 17 – Patriarch Nikon of Moscow, Patriarch of the Russian Orthodox Church (b. 1605)
- August 18 – Thomas Allen, English politician (b. 1603)
- August 22 – Philippe Delano, Dutch Plymouth Colony settler (b. 1602)
- September 11 – Godfrey Henschen, Jesuit hagiographer (b. 1601)
- September 16 – Jahanara Begum, Mughal princess (b. 1614)
- September 27 – Jacob Masen, German poet (b. 1606)
- October 7 – Nikolaes Heinsius the Elder, Dutch scholar (b. 1620)
- October 15 – Johann Ludwig Schönleben, Carniolan priest (b. 1618)
- November 2 – Eleanor of Anhalt-Zerbst, duchess by marriage of Schleswig-Holstein-Sønderburg-Norburg (b. 1608)
- November 13 – Arnold Braemes, English politician (b. 1602)
- November 17 – Tito Livio Burattini, Italian inventor, Egyptologist and instrument-maker (b. 1617)
- November 26
- December 4 – Maurice, Duke of Saxe-Zeitz (b. 1619)
- December 12 – Hermann Conring, German philosopher (b. 1606)
- December 15 – James Compton, 3rd Earl of Northampton, English politician (b. 1622)
- December 16 – François Vavasseur, French writer (b. 1605)
- December 18 – Olimpia Aldobrandini, Italian Aldobrandini family member, heiress (b. 1623)
- December 21 – Lacuzon, Franche-Comte military leader (b. 1607)
- December 22 – Richard Alleine, English Puritan clergyman (b. 1611)
- date unknown