Striker Fletcher sustained an ankle ligament injury while on international duty with Scotland and his absence will be a big blow for the struggling Black Cats.
The 26-year-old has featured in all but two of Sunderland's Premier League matches this term and is the club's leading goal scorer with 11 goals.
Club captain Cattermole has undergone surgery on the knee injury that has dogged him all season, restricting him to just 14 appearances in all competitions.
A statement on the club's website read: "Cattermole underwent an operation on his knee 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."