Vilanova's former players led the tributes to a man who, alongside Pep Guardiola, helped mould them into one of the best teams in the history of the game.
Vilanova led the club during the 2012/13 season after taking over from Guardiola, having spent four trophy-laden years as his assistant, but was forced to resign last July because of ill health
Vilanova, who as assistant helped Barca win three Primera Division titles and two Champions League crowns, was first diagnosed with parotid gland cancer in November 2011 and the disease returned in December 2012.
He was away from the team from December, undergoing surgery and treatment in New York as his assistant Jordi Roura took charge in his absence, but returned in late March and still won the La Liga title again - and with a record points haul - before stepping down in July last year.
Messi, the star of his team, said on his Facebook page alongside a picture of the pair together: ''I will never forget Tito. Forever with you. All my love to his family.''
Vilanova and Guardiola formed their friendship as players in Barca's youth set-up. Although Vilanova never played a first-team game for the club, instead spending his career largely in the Spanish second division, he linked up again with Guardiola when the latter took over the Barcelona B team in 2007.
The club's president Josep Maria Bartomeu said his death had left everyone at the club "feeling very empty".
"He's been an example to us and we have all learnt a lot from him as a person. We will miss him terribly," he added on the club website.
Barca's sporting director Andoni Zubizarreta added: " We have lost a true Barca man who knew this club from the old Masia (Barca's youth academy) to the changing rooms, from the Barca B manager's job in the third division to becoming the first-team coach.
"He looked his illness straight in the eye - as he did everything he undertook. A marvellous man has passed away and now we have to give his family all our support."
Midfielder Andres Iniesta said on Twitter: ''I have no words. You have been and will be an example, proud to be part of your life. I'll never forget."
Vilanova was reportedly admitted to hospital in Barcelona on Thursday after his health deteriorated rapidly, leaving him needing an operation on his stomach.
Barca announced his death with ''immense sorrow'' and said they would open a space in the main grandstand at the Nou Camp for people to express their condolences.
Flags at the stadium were flown at half mast.
A minute's silence will be held before all matches in Spain's top two divisions this and next weekend in honour of Vilanova. His funeral will take place at 8pm on Monday at Barcelona Cathedral.
Mourinho said on Chelsea's Twitter account: ''Tito Vilanova's passing is a sad day for football, for Barcelona and most importantly for his family and friends.
''On behalf of everybody at Chelsea Football Club I send my deepest condolences at this most difficult time.''
Florentino Perez, the Madrid president, expressed his " deep sorrow" on behalf of Barca's great rivals.
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