The midfielder says the Catalans will struggle to replace the Argentine ace, who has been sidelined for up to eight weeks with a hamstring injury.
The Argentina international suffered a hamstring injury in the Blaugrana's 4-1 defeat of Real Betis on Sunday and could be out of action until after the winter break.
The reigning champion still heads the Primera Division table by three points, but Xavi suspects that the club will need its star man back as soon as possible.
"Everybody knows the importance of Leo to this team," the 33-year-old told Mundo Deportivo. "Leo makes the difference and there is no player in the world capable of doing what he does.
"But he will be ok. He will be back and it will be great to have him playing again."
Gerardo Martino's side has eight games to play in three different competitions over the next six weeks before the Spanish season embarks on its winter break.