The former coach succumbed to his battle with cancer, having been hospitalized following a downturn in health that required emergency surgery.
The onetime midfielder was admitted to the hospital following a downturn in his health that required an operation on his stomach Thursday, with club president Josep Maria Bartomeu confirming Vilanova was "fighting" for his life.
Vilanova, whose post-playing career was tragically cut short by cancer, was unable to battle any longer and passed away Friday afternoon.
His health problems became public after he suffered a relapse of parotid gland cancer in 2012 — a year after his original diagnosis, and just six months into his tenure as head coach at Camp Nou as Pep Guardiola's successor.
He underwent surgery in December 2012, with Jordi Roura taking his place on the bench while he recovered in New York, before returning in March 2013 to see out the rest of the reason and guide Barca to La Liga victory.
However, his continued health woes saw him unexpectedly step down as coach of the Catalans last summer, with Gerardo Martino taking the reins in his place.
Following confirmation of Vilanova's death, Barcelona president Bartomeu said in a news release: "Tito will be reference as a man and in terms of football for Barcelona forever. We thank him for everything he taught us. Rest in peace."
The Catalans, whom Vilanova worked under for years before being promoted to head coach in 2012, also sent their condolences to the family.
"The club wishes to express its most heartfelt sympathy to his family, who are being joined in these moments of mourning by Barcelona members and fans all around the world, as well as the rest of the footballing and sporting world. The Vilanova family has asked for respect for their desire for the strictest intimacy in the moments after his death."
Vilanova is survived by a wife and two children.