The veteran midfielder – who turned 35 last Sunday - is out of contract in June and looks set to take no further part in the club's battle to remain in the Premier League.
Duff has made 173 appearances for Fulham since joining from Newcastle United in 2009, the most he has played for one club during a career that also included spells at Blackburn Rovers and Chelsea.
"We have to expect that he will not play this season anymore," said Fulham manager Felix Magath.
The loss of a creative player like Duff is an undoubted blow to Fulham's chances of staving off the threat the relegation.
Magath's men prop up the rest of the Premier League and have the chance to leapfrog over Cardiff City should the London club win in the Welsh capital on Saturday.
Ahead of a crucial juncture in Fulham's season, Magath has backed his players to stay up.
"I'm convinced that we will avoid relegation because we have developed in the last 14 days (since he took charge) and the team is growing together and that is what makes me sure," he said at his pre-match press conference ahead of the Cardiff game.
"We have a quite good schedule in the last 10 games.
"I get the feeling here that everybody knows that everybody sleeps well with this knowledge that are games ahead of us that we can win."
And Magath insists the pressure is all on Cardiff as he goes in search of his first win since succeeding Rene Meulensteen at Craven Cottage.
He added: "Cardiff has a home game and they have to win. They are one point better than us, that is not enough for them, they have go to higher to avoid relegation.
"It is very important for us to have the first win. Now is the time to fight.
"Teams need confidence and the best confidence you can get is if you win. These three points are very important to us, not only to step up from last place. We need a win for ourselves and our confidence."
