The president of the European Parliament, David Sassoli, died early on Tuesday at a hospital in Italy, his spokesman has said.
The 65-year-old Italian had been seriously ill for more than two weeks due to an immune system condition.
"David Sassoli passed away at 1.15am on January 11 at the CRO in Aviano, Italy, where he was hospitalised," spokesman Roberto Cuillo wrote on Twitter. "The date and place of the funeral will be communicated in the next few hours."
The former television newsreader had been in hospital since December 26, with "a serious complication due to a dysfunction of the immune system", Mr Cuillo had said on Monday, announcing the cancellation of Sassoli's official activities.
Sassoli was also admitted with pneumonia for several weeks last September.
The European Parliament sits for a five-year term between elections but its president 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.
Known as 'Il Presidente'
After a 30-year career as an Italian journalist, starting out in newspapers then moving to television and becoming a well-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 during public appearances, Sassoli made a point of using Italian.
On Tuesday next week, MEPs are expected to hold the first round of voting for his successor.
Maltese politician Roberta Metsola, from the conservative European People's Party (EPP), is widely expected to be a candidate for the post.
'An outstanding president'
European Commission President Ursula van der Leyen, who heads the European Union's executive body, paid tribute to Sassoli, and said she was deeply saddened by his death.
"David Sassoli was a compassionate journalist, an outstanding President of the European Parliament and, first & foremost, a dear friend," she said on Twitter.
Nato Secretary General Jens Stoltenberg sent his condolences.
"Saddened to hear of the death of EP President David Sassoli, a strong voice for democracy and NATO-EU cooperation," he said in a tweet.
Italian politicians on many sides paid tribute to Sassoli, and his death dominated morning news shows. Prime Minister Mario Draghi said his passing was shocking and praised him as profoundly pro-European.
"Sassoli was a symbol of balance, humanity and generosity. These qualities have always been recognised by all his colleagues, from every political position and every European country," Mr Draghi's office said.
Former prime minister Enrico Letta, who heads the Democratic Party, called Sassoli "a person of extraordinary generosity, a passionate European ... a man of vision and principles".