Bayern Munich are looking to close the two-point gap behind German league leaders Borussia Dortmund and face up to life without Bastian Schweinsteiger when they host Kaiserslautern on Saturday.
The Germany star and Bayern vice-captain has only played three Bundesliga matches since returning from a broken collarbone, but he twisted his ankle in Wednesday's 2-0 German Cup win at Stuttgart and damaged ligaments.
His foot is in a protective cast and he looks to be out for several weeks, with Bayern to face FC Basel in the Champions League Round of 16 in a fortnight.
"This is a bitter blow for him, it's incredibly sad," said coach Jupp Heynckes.
"And it's also bad for us as a team, he is a very important player."
Second-placed Bayern have two relatively easy Bundesliga matches coming up against Kaiserslautern, who are third from bottom, and next Saturday travel to tailenders Freiburg, before they take on Basel then Schalke.
Heynckes is most likely to slot Anatoliy Tymoshchuk in for Schweinsteiger alongside Brazil's Luiz Gustavo at the back of the midfield.
He also seems to have settled on the preferred defence of Jerome Boateng and Holger Badstuber as the centre-backs with Philipp Lahm and Rafinha on the wings.
But Bayern's confidence is shaken after picking up just four points from nine in their last three league games and need a confidence-boosting win over a Kaiserslautern team which has not won in the last ten games.
Leaders Borussia Dortmund are flying high after their 2-0 win at Nuremberg last Friday saw them go top of the league and look to have striker Lucas Barrios back in form after scoring in both of his last two games.
Jurgen Klopp's side have won all three league games so far in 2012 and host a Leverkusen team which tackles Champions League holders Barcelona on Tuesday in the first leg of the Round of 16.
With his side sixth in the league, Leverkusen coach Robin Dutt has had to cope with the loss of important squad members Sidney Sam and Eren Derdiyok through injury, while defender Michal Kadlec is banned after being sent off last weekend.
Midfielder Renato Augusto is back from injury and Croatia defender Vedran Corluka has impressed since joining from Tottenham Hotspurs.
"They are an incredibly strong opponent, we're going to meet a really good football team," said Klopp.
Dortmund are likely to be without midfield trio of Jakub 'Kuba' Blaszczykowski (groin), Kevin Grosskreutz (back) and Ilkay Guendogan who are all carrying injuries.
But after their impressive 4-0 win at fourth-division Holstein Kiel in the German Cup, Dortmund are in form and have win their last six games.
Arguable the clash of the weekend is third-placed Schalke up against fourth-placed Moenchengladbach.
Gladbach, under Swiss coach Lucien Favre, have undergone a remarkable turn around. Having only avoided relegation by the skin of their teeth last season, they are challenging the leaders.
They are only three points behind Dortmund and beat Schalke 3-1 in the third round of the German Cup last December.
"I have lots of respect for Lucien Favre, he has put together a very good team," said Schalke coach Hubb Stevens.
"Gladbach's strength is their good defence, but they are also very quick to counter-attack."
Hoffenheim, eighth in the table, are at fifth-placed Werder Bremen on Saturday without coach Holger Stanislawski, who was fired on Thursday after their shock German Cup exit at home to second division Greuther Fuerth.
Ex-Stuttgart and Hertha Berlin coach Markus Babbel is tipped to take over.
VfL Wolfsburg v Freiburg
Borussia Dortmund v Bayer Leverkusen
Mainz 05 v Hanover 96
Bayern Munich v Kaiserslautern
Werder Bremen v Hoffenheim
VfB Stuttgart v Hertha Berlin
Borussia M'gladbach v Schalke 04
Augsburg v Nuremberg
Cologne v Hamburg