The 29-year-old's absence will provide a timely boost to the tourists as they head to Edgbaston for the third Test trailing 1-0 in the five-match series.
Ian Bell looks set to replace his fellow right-hander but a Test average against Australia of 20.10 - dwarfed by Pietersen's 50.72 - does not bode well.
Adding to England's worries, key all-rounder Andrew Flintoff is struggling with the knee injury which will see him retire from Tests at the end of this series.
BBC Sport spoke to several ex-England players to assess the potential impact of Pietersen's absence.
CAN ENGLAND STILL WIN THE ASHES?
England's most capped player and former captain Alec Stewart: "I wouldn't say it dramatically reduces England's chances. You have to remember Pietersen hasn't had a huge bearing on the two Tests so far.
"That said, England have lost someone who has that X-factor and someone who can take the game away from Australia in the space of an hour or a session.
"As an ex-England player and England fan, I hope and expect us to go on and regain the Ashes."
Former England captain Graham Gooch: "It's a loss in the sense that Pietersen has a big presence - he's a box office player and has a fantastic record for England in the four years he's been playing.
Bell has been in fine form for Warwickshire but has a mixed record against Australia
"On the one hand you'd think this is a big loss but sometimes when one door closes another opens for someone else. It's not about Pietersen now - injuries are part of a professional sportsman's life and a team has to cope with that."
Former England captain Mike Gatting: "The blow for England is having one of your major batsmen drop out for the whole series, not just for one match.
"But if you're a good side you've got to learn to play without some of your best players at times and if that's what England are striving for they've got to come through this test.
"KP is a very, very fine player but we've got some other good young lads in the side and they've got to show their worth. You can't just keep relying on one person."
Former Australia batsman Dean Jones: "The major priority for Australia is getting Mitchell Johnson right. If he bowls half-decent we'll really worry England. Secondly, they will enjoy bowling at Edgbaston because the run-ups are different, there a no slopes, it's a flatter ground and it doesn't have the aura of Lord's. Even thought we have a poor record at Edgbaston I'm expecting us to come back bigger, better and stronger."
What you say: "England are not guaranteed to win at all, I think it will be very close." -
Trebell on 606
WHO WILL REPLACE PIETERSEN IN THE SIDE?
Graham Gooch: "Ian Bell will probably come in but, more importantly, all of the other players will look at themselves and think, 'Right, I've got to step up my game, I've got to raise the bar a bit and we've got to fill the void'."
Mike Gatting: "The selectors have had Bell in the squad in the last two Tests so one would assume he would come in, perhaps at three, and let Ravi Bopara go down to four. Certainly Bell would be many people's choice."
What you say: "What about Stephen Moore as another option? He got a ton against the Aussies in the Lions game. The trouble with all the other names is they've all been there and failed!" -
No More Sweeping on 606
DOES IAN BELL WARRANT A PLACE IN THE TEAM?
Alec Stewart: "Ian Bell is a fine player, a different type of player but someone who has experienced success. He doesn't destroy an attack, he will just bat his way to a big total. I am backing him to do exceptionally well if he comes in to replace Pietersen."
Graham Gooch: "It would be good for Ian Bell to come in, especially on his home patch. He's been out of the side for a few months now because people have accused him of not going on and converted his good starts, but he's been averaging 80 this domestic season.
"This is a chance to prove those doubters wrong. Technically he's a good player - now he can show he's improved, he can go out there and stamp his authority and that's what everyone wants Ian Bell to do."
Mike Gatting: "He's shown he can get hundreds in Test cricket - he's been out for a little while and I'm sure he'll be very fired up to make an impression, especially against the Australians, who he probably owes a few runs."
What you say: "He has always looked out of it in Test cricket, particularly against strong opposition. He was one of the few weak links in the 2005 team." -
Champion1971 on 606
HOW WILL PIETERSEN'S ABSENCE AFFECT THE AUSTRALIANS?
Dean Jones: "We're of the thinking that if England lose this Test series we don't want to say we've beaten you with an under-strength team. We'll take a win - don't worry about that - but we'll know in our heart of hearts you might not have had your best team."
Former England seamer Angus Fraser: "When you lose one of your key players you are more vulnerable. We saw that in 2005 when Glenn McGrath twisted his ankle just before the Edgbaston Test and England were able to exploit that.
England are sweating on the fitness of second Test hero Andrew Flintoff
"One of Australia's problems has been bowling England out in this series and the departure of Pietersen means there is a poorer and more vulnerable player stepping into his place. Ian Bell is a wonderful cricketer but he is not in Pietersen's class."
Alec Stewart: "It is a big blow to England. He is their best batsman, he is a match-winner, and he is someone Australia will be pleased to see the back of."
What you say: "The bowling attack as it stands is poor for an Australian one if we were fortunate enough to win a third toss and bat I fancy their already flaky bowling would crumble without the protection of say 450-500 runs." -
ggatsby on 606
COULD THE ENGLAND AND WALES CRICKET BOARD HAVE HANDLED THE INJURY BETTER?
Alec Stewart: "It's vital that the powers that be at the ECB make sure they are in charge of the player and the player isn't in charge of their employers. The ECB are aware of all the money at the IPL and of course the players want to go their.
"As long as they realise England must come first when they sign that contract then I'm all for the central contract because then the ECB can control when their players play, when they rest and when they practice."
Angus Fraser: "The central contract system has worked. The best cricketers in this country now spend most of their time playing for England."
What you say: "The correct decision for the long term was made. If the Achilles did snap then that is a different matter all together so KP has done the right thing and can get ready for the future series like South Africa." -
jazzman_jackson on 606
HOW IMPORTANT IS IT THAT ANDREW FLINTOFF NOW STAYS FIT ENOUGH TO COMPLETE THE SERIES?
Graham Gooch: "You want Flintoff because he's such an outstanding performer with the ball and gives presence to the side. He gives that punch to the attack. They're using him as a spearhead to the bowling now and that's the right way to use him up front against the Australian left handers.
"His presence will be missed if he's not playing. But you can't take a half-fit guy onto the field. They'll be working overtime to try and get him in some sort of shape not only to get him through Edgbaston but the last 15 days of this Ashes series."
Alec Stewart: "I saw him on Tuesday night and he is very hopeful. His body is a bit sore but with the right amount of rest, and good medical treatment, he is doing his rehab and is desperate to play in all three Tests.
"He is key, he certainly played his part in winning the second Test and I am backing him to play in all three Tests."
What you say: "The simple fact is Freddie is injury prone and since '05 Ashes has been inconsistent compared to the more consistent KP who rarely has had a bad series." -
greyblazersghost on 606
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