The president of the European Parliament, David Sassoli, died early Tuesday in hospital in Italy, his spokesman said on Twitter.
The 65-year-old Italian had been seriously ill in hospital for more than two weeks due to a dysfunction of his immune system.
"David Sassoli passed away at 1.15am on 11 January at the CRO in Aviano, Italy, where he was hospitalised," his spokesman Roberto Cuillo tweeted.
"The date and place of the funeral will be communicated in the next few hours."
Maltese MEP Roberta Metsola, who is the frontrunner to succeed Sassoli as EP president, said she was heartbroken by the news.
"Europe has lost a leader, I have a lost a friend, democracy has lost a champion. David Sassoli dedicated his life to making the world a better, fairer place," she wrote.
A former television newsreader, Sassoli had been in hospital since December 26 due to "a serious complication due to a dysfunction of the immune system," Cuillo had said on Monday, announcing the cancellation of Sassoli's official activities.
Sassoli was previously admitted with pneumonia for several weeks last September.
The European Parliament sits for a five-year term between elections, but the president of the body serves for half that time.
Sassoli had already indicated that he would not seek re-election.
He was born on May 30, 1956, in Florence, Italy.
After a three-decade career as an Italian journalist, starting out in newspapers then moving to television and becoming a nationally known anchor, Sassoli became a member of the European Parliament in 2009, and speaker in 2019.
He was a member of the centre-left Progressive Alliance of Socialists and Democrats, the second-biggest grouping in the parliament after the centre-right European People's Party.
Although his role was that of speaker, he had the title of president of the European legislature. His arrival in the chamber was traditionally announced in Italian as "Il Presidente".
Unlike some EU officials, who speak in English and French in public appearances, Sassoli had made a point of using Italian.
Sassoli died just as his term as EP president was due to end. MEPs are due to hold the first round of voting for his successor on Tuesday next week, with Metsola the frontrunner.
In a statement, the Nationalist Party expressed its condolences and said Sassoli would be remembered as a man who placed Europeans' interest first.