Borussia Dortmund were dealt a double injury blow for Saturday's key Bundesliga showdown against Bayern Munich with both defenders Mats Hummels and Marcel Schmelzer ruled out with injury.
The pair limped out of Germany's 1-0 friendly win over England on Tuesday.
Scans on Wednesday revealed centre-back Hummels is out until 2014 with a torn ligament in his right ankle, while left-back Schmelzer is sidelined for three weeks with a torn left calf.
"Bad news for me today. I won't be able to play any more this year so all I can do is support the guys in the next weeks," Hummels wrote on his Facebook page.
"It will be very difficult, but I am optimistic we can make it through these games."
The timing is bad for Dortmund, who must beat Napoli at home in the Champions League next Tuesday, then Marseille away on December 11, to keep alive their dreams of reaching the knock-out stages.
With Hummels' centre-back partner Neven Subotic out for six months with torn knee ligaments and right-back Lukasz Piszczek only just back from surgery, it means Dortmund face the European champions without their entire first-choice back four.
Subotic's possible replacement, ex-Germany defender Manuel Friedrich, 34, who was released by Bayer Leverkusen at the end of last season, picked up an injury in a practice match on trial with Dortmund on Tuesday, according to German daily Bild.
Having come on as a second-half replacement at Wembley, Hummels lasted just 20 minutes on Tuesday while Schmelzer played the first-half against England and was taken off at half-time.
Dortmund's director of sport Michael Zorc has complained about the scheduling of the game against Bayern.
"As far as I am concerned, this is unfortunate scheduling," said Zorc.
"To play this match just before another round of Champions League games and after a long international break, is not optimal, in terms of preparation, for the anticipation, for all of it, for all parties involved."
With European champions Bayern four points clear in the league and already in the knock-out phase of the Champions League, Munich coach Pep Guardiola has no such injury concerns.
Dutch wing Arjen Robben has recovered from a small knock while on international duty, while centre-back Jerome Boateng is fit to play despite being taken off after half-time at Wembley with a minor heel injury.
Having rested both Bayern stars Philipp Lahm and Manuel Neuer for the England match, Germany coach Joachim Loew said he regretted the injuries to Dortmund's Schmelzer and Hummels.
Real Madrid also lost Germany star Sami Khedira, in last Friday's 1-1 draw with Italy, for the next six months with a knee injury.
"When players are injured during international matches, it is always regrettable for the player, the club and the national team," said Loew.
"Marcel and Mats were in good shape and the fact this has happened is, of course, unhappy news for Dortmund.
"If you also include the bad injury to Sami Khedira, I can't remember the last time we have had so many injuries in such a short period.
"Just like with Sami, I wish Mats and Marcel a speedy recovery and hope to see them on the field again soon."