The 22-year-old has been ruled out until April at the earliest after rupturing a cruciate ligament during pre-season. Clarke was injured just two minutes into Blackpool's first summer friendly against Tiverton Town on July 16 and it was initially thought he would be out for three months.
However, the problem is worst than first feared and the player has now undergone surgery. Manager Ian Holloway said: "It might be the whole season now. He was looking so sharp in training and had done so much in the summer to try and get over the knocks he had last year.
Holloway added: "We're all gutted for him, absolutely gutted for him."
In a further blow for the Seasiders, forward Louis Almond has been ruled out for up to three months with a dislocated shoulder.
Almond, 18, who had a spell on loan at Cheltenham last season, is also to have an operation after suffering the injury against Leyton Orient in Saturday's pre-season clash in Devon.
The injuries further reduce Holloway's options in a threadbare squad.
Holloway is yet to sign a player this summer while four key men from last season's Championship play-off success are no longer at Bloomfield Road.
Seamus Coleman, DJ Campbell and Stephen Dobbie have all returned to their parent clubs after loans while Ben Burgess has moved to Notts County.
Former Everton and Arsenal striker Francis Jeffers has been on trial with the Tangerines while Holloway is thought to be closing in on a deal for Israel defender Dekel Keinan.
Charlie Adam believes he got lucky by quitting Glasgow giants Rangers for Blackpool.The 24-year-old raised eyebrows last year when he swapped a tilt at the Scottish Premier League title for a side expected to struggle in the Championship.
His decision has now been spectacularly vindicated after Blackpool - with Adam as the stand-out player - overturned huge odds to win a place in the Barclays Premier League via the play-offs.
Adam says Tangerines boss Ian Holloway has got the best out of him and he now feels his career can only benefit from playing in England's top flight."You always have to make decisions and sacrifices in life and I have done that," Adam said.
"It might not have worked but I'm lucky, it did."I have a manager who trusts me and shows great faith in being able to play football and that is important."
Source: PA