Recent Bundesliga champions Stuttgart, Wolfsburg and Werder Bremen are fighting relegation, and need to win this weekend to boost hopes of avoiding the drop.
Stuttgart, the 2007 champion, is playing under its third coach of the season, sits second from the bottom and is four points from safety with 12 games left to play. The team hosts second-place Bayer Leverkusen on Sunday.
Goal difference separates 2009 champion Wolfsburg from the relegation playoff place ahead of Saturday's trip to Freiburg.
Werder Bremen, the 2004 champion, is only one point above. It travels to Hamburger SV for the 94th Northern Derby, also on Saturday.
Experience should not be a problem for the three sides. Wolfsburg has 13 players in its squad who were involved in relegation battles with other clubs - seven of whom were relegated. Werder has 11, and Stuttgart has eight.
Both Stuttgart and Leverkusen are still involved in the Europa League, and Stuttgart coach Bruno Labbadia hopes the distraction of European action will have benefits for his side.
"Of course we are in a very difficult situation in the Bundesliga but we have to put that to the side," the 45-year-old Labbadia said ahead of Thursday's first leg match against Benfica. "We want to take something positive (from it)."
Russia striker Pavel Pogrebnyak leads the list of injuries after breaking a rib in training, although Japan striker Shinji Okazaki could make his debut following his signing from Shimizu S-Pulse.
Michael Ballack is ruled out for Leverkusen with a knee injury. Coach Jupp Heynckes has not indicated when he expects the midfielder back, but is in no hurry following last weekend's comprehensive 3-0 win at Eintracht Frankfurt.
Wolfsburg coach Pierre Littbarski, seeking his first win since taking over from Steve McClaren, sent his players a signal by sending Alexander Madlung and Thomas Kahlenberg home from training for a lack of effort.
"We need players who are 100 percent committed and who identify with the club," Littbarski said.
Diego, suspended by the coach for last week's home loss to Hamburg, returns for the trip to sixth-place Freiburg.
Werder Bremen travels to Hamburg on the back of six-game losing streak away from home, more than any other in the Bundesliga.
Hugo Almeida, who scored twice for Werder in a 3-2 win when the sides last met, was sold in the winter break to Besiktas - a decision which Klaus Allofs may regret. Almeida remains Werder's top scorer with nine goals.
Claudio Pizarro remains doubtful with a muscle injury, but Bremen will hope he can play. The Peruvian is the top scoring foreign striker of all time in the Bundesliga with 137 goals, and Werder has collected 17 points from 13 games in which he has played. Without him, there was only one win from nine.
On Friday, Nuremberg hosts Eintracht Frankfurt, which has yet to score in 2011.
After two draws in a row, leader Borussia Dortmund hosts 11th-place St. Pauli on Saturday. St. Pauli's win in the Hamburg derby made it three in a row and it remains unbeaten in 2011.
Also Saturday, it's: Hoffenheim vs. FC Cologne; Hannover vs. Kaiserslautern; and Bayern Munich vs. Mainz.
Bayern plays at Inter Milan on Wednesday in the Champions League in a repeat of last year's final, and then hosts Dortmund next weekend.
After Leverkusen hosts Stuttgart on Sunday, Lucien Favre's first game in charge of bottom side Borussia Moenchengladbach is at 10th-place Schalke.
Favre took over on Monday, a day after Michael Frontzeck was fired, and has 12 games to save Moenchengladbach, seven points from safety having conceded 56 goals - easily the Bundesliga's worst defensive record.
"It's a team problem, not just one of defence," Favre said. "We still have the chance to stay in the Bundesliga."