The Italy international will have surgery next week after damaging knee ligaments in last Sunday's 1-0 win over Catania and risks missing the rest of the season.
"This injury was a big surprise for us. On Sunday he finished the game and he was fundamentally important for us, as always," forward Andriy Shevchenko told the club's in-house TV channel. "He is a leader for us. We'll miss him a lot."
In theory, Milan have plenty of back-up in Emerson, Mathieu Flamini and Massimo Ambrosini.
Although Emerson and Flamini are good readers of the game, they lack Gattuso's dynamism and ability to cover so much ground in 90 minutes.
Ambrosini is the most natural stand-in.
TACTICAL CHANGES
But coach Carlo Ancelotti regularly fields them both in his starting lineup, with Gattuso operating predominantly across the width of the pitch to plug gaps and Ambrosini going forward more to pressure opponents in possession and support attacks.
Gattuso's loss will inevitably cause tactical changes, although he would not have been able to play this weekend anyway because of suspension.
The omens for Milan are not great as the player was missing in the three defeats they have suffered so far in Serie A.
Ambrosini has had injury problems of his own and has missed several recent matches. He is expected to be available on Sunday though, as he was able to train with his team mates on Wednesday.
Fellow midfielder Andrea Pirlo and forward Ronaldinho are tipped to come back too after missing the Catania game with fitness problems, but Clarence Seedorf remains an injury doubt.
Juventus captain Alessandro Del Piero is set to return to the starting lineup after missing Sunday's 2-1 win at Lecce with a muscle strain. Del Piero came on in the second half of Wednesday's goalless draw with BATE Borisov in the Champions League.
Italy midfielder Mauro Camoranesi should be able to return too despite a shoulder knock, coach Claudio Ranieri said following the BATE game, but defender Nicola Legrottaglie is suspended.
Champions Inter Milan, who have a six-point lead over joint-second Milan and Juve, will look to make ground on at least one of their rivals by collecting their seventh consecutive league win at home to bottom side Chievo Verona earlier on Sunday.
