Throat cancer had forced Pep Guardiola's successor to step down from post last summer
Vilanova led Barcelona during the 2012/13 season after taking over from Pep Guardiola, but was forced to resign last summer because of ill health.
Messages of condolence poured in from around the world for a man who also spent four years as Guardiola's assistant at the Nou Camp, playing a key role in coaching one of the greatest teams of all time. Barca won three La Liga titles, two Champions League crowns and two Fifa Club World Cups under the duo.
Vilanova 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: "A person difficult to forget. I will always remember you. All my love to the family of Tito."
Vilanova, a former midfielder who spent his playing career largely in the Spanish second division, first assisted Guardiola with the Barcelona B team before the pair stepped up to the first XI. Their team became renowned for their passing and pressing game, with midfielders like Xavi and Andres Iniesta at its heart.
In sole charge, Vilanova led Barca to their highest ever points total for a La Liga season during his single season in charge, their 100 points a joint record for the division with Real Madrid.
Iniesta posted a picture of himself with Vilanova on Twitter, writing: "I have no words. You have been and will be an example, proud to be part of your life. I'll never forget. Much strength to your family. Rest in peace coach. Kiss."
Barca midfielder Cesc Fabregas paid an emotional tribute on his Facebook page. He wrote: "Tito, thank you for all you have given to football and Barca. Personally, I met you 14 years ago and I can say that there are very few people like you. Thank you for always trusting me to help me improve and overcome personal and professional obstacles. We will always keep a place for you in our hearts. Rest in peace Tito."
Barca sent their "deepest condolences" to Vilanova's family and said they would be opening a space in the main grandstand at the Nou Camp for people to express their condolences. The club's president, Josep Maria Bartomeu, said on Twitter: "Tito Vilanova was a wonderful person, and will never be forgotten at FC Barcelona. Thank you for everything you taught us. Rest in peace."
The Spanish Football Federation said Vilanova would "always be linked to a unique generation of players".
He said in a statement: "I want to express my deep sorrow at the death of Tito Vilanova and transmit, on behalf of Real Madrid, our condolences, love and support to his family, to FC Barcelona and most especially his wife and children. Today is a day of great sadness for all football fans and recognition of his personal and professional career."
Chelsea boss Jose Mourinho had several run-ins with Vilanova during his time in charge of Real Madrid, infamously poking him in the eye in one clash. 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."
Madrid defender Sergio Ramos added on Twitter: "Lots of support to all of Tito's family and friends. An example of fighting and strength for all of us. RIP."
Madrid's former player Michel Salgado played alongside Vilanova for Celta Vigo, where Vilanova spent three seasons from 1992 to 1995.
"Destroyed over Tito Vilanova's death, my condolences to family and friends and such a big honour having played with him in Celta," he said.
Florentino Perez, the Real Madrid president, paid tribute to Vilanova on behalf of Barca's great rivals.