Tito Vilanova is stepping down as coach of Barcelona to continue his treatment for cancer, club president Sandro Rosell has confirmed.
Vilanova only replaced Pep Guardiola last summer, and during his first season in charge after replacing the club's most successful ever manager, oversaw the club regain the La Liga title from Real Madrid.
However, Vilanova's reign has been overshadowed by health concerns.
Vilanova had a tumour removed from his throat in late 2011, but suffered a relapse a year later. He underwent another operation on his parotid gland in December before beginning a course of chemotherapy and radiotherapy in New York.
"We are here to give you some news that I would have liked never to have had to give," said a grim-faced Rosell, adding that the club had decided to cancel Saturday's friendly against Polish side Lechia Gdansk.
"Life goes on, this is a very severe blow but Barca always comes through and this time it will be no different," Rosell said.
Only on Tuesday, in his first news conference since the players returned from holiday, he spoke of his excitement about the new season and the prospect of seeing new signing Neymar playing alongside World Player of the Year Lionel Messi.
As messages of support flowed in on Twitter from both within and beyond the sporting world, including from Barca's arch rivals Real Madrid, speculation began about who the club would target for one of the most sought-after jobs in world soccer.
Barcelona-based newspaper Sport and other media reported that Joan Francesc Ferrer, known as "Rubi", may be in line to take over.
Ferrer led Girona to the second division playoffs last season and was appointed Vilanova's assistant for the coming campaign to help with technical analysis of Barca's rivals.
Other names mentioned, all former Barca players, included Swansea manager Michael Laudrup, Celta Vigo's Luis Enrique and Ajax's Frank de Boer. Andre Villas-Boas, manager of Tottenham Hotspur, was also considered a possible candidate.
Last season, Vilanova helped Barca to a fourth La Liga success in five years as they equalled Real Madrid's record points haul from the previous term of 100.