Sunderland have announced Steven Fletcher and Lee Cattermole are out for the season.
Leading scorer Fletcher suffered ankle ligament damage on international duty with Scotland last week, and midfielder Cattermole underwent surgery on a persistent knee problem on Wednesday.
A club statement said: "Sunderland have confirmed today that striker Steven Fletcher and captain Lee Cattermole will miss the rest of the current campaign due to injury."
The statement added: "Cattermole underwent an operation on his knee earlier today and Fletcher sustained ankle ligament damage whilst on international duty with Scotland.
"It is not known at this stage if Fletcher will require an operation, with the injury requiring further assessment in the coming weeks.
"Both players will play no further part in the Black Cats' 2012-13 Barclays Premier League season."