Everton will be without the influential Marouane Fellaini for the remainder of the season while Tim Cahill will be out for at least two weeks.
The Belgium international, who will undergo ankle surgery next week, did not feature in the Toffees' surprise FA Cup defeat to Reading on Tuesday and manager David Moyes confirmed the news after the match.
Fellaini aggravated the injury in Saturday's 2-0 weekend success over Sunderland and he will not take part again for Everton this term.
"Marouane is going to be out for the season now, he will have an operation on Monday," confirmed Moyes.
With Everton now out of the FA Cup, Moyes' only task is ensuring the club retain their Premier League status and they currently sit 11th in the table five points clear of third from bottom Wolves.
In a double blow for Everton, Moyes also confirmed after the full-time whistle that talisman Cahill would also be sidelined for at least two weeks with a foot problem.
Moyes added: "Everybody who has watched us will tell you he has been a key player for us and Tim Cahill will probably miss two or three weeks as well."