Sassoli was seriously ill in hospital for more than two weeks due to a dysfunction of his immune system.
The president of the European Parliament, David Sassoli, died in hospital in Italy.
"David Sassoli passed away at 1.15 am on 11 January at the CRO in Aviano, Italy, where he was hospitalized," his spokesman Roberto Cuillo tweeted on Tuesday.
"The date and place of the funeral will be communicated in the next few hours."
The @EP_President David Sassoli passed away at 1.15 am on 11 January at the CRO in Aviano( PN), Italy, where he was hospitalized. The date and place of the funeral will be communicated in the next few hours.— RobertoCuillo (@robertocuillo) January 11, 2022
The 65-year-old Italian had been seriously ill in hospital for more than two weeks due to a dysfunction of his immune system.
The former television newsreader 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.
On Tuesday next week, MEPs are expected to hold the first round of voting for his successor.