Andre Schurrle and Christian Pulisic will return to the Borussia Dortmund squad for the derby against Schalke on Saturday.
"It's like a cup final," coach Thomas Tuchel said. "You only have this one chance to win it and otherwise you have to wait for one year."
Partly because of major injury troubles at the Westfalenstadion, Dortmund have only picked up two points from their past three Bundesliga games and dropped to sixth in the standings, six points behind leaders Bayern Munich.
On the other side, Schalke, their guests on Saturday, have not lost a competitive match in six across all competitions, and though they are only ranked 14th enter the derby full of confidence.
"It's simply the derby in Germany. It's a gift to be a part of it, and to be so close to it. It's a special match. It feels different," said Tuchel, who will stand on the sidelines of the fixture for the third time, told his prematch news conference on Friday.
The Dortmund boss added that a win would be "mega important" after the last couple of weeks.
Dortmund struggled in their mid-week cup fixture against second-tier club Union Berlin and only escaped a major upset in a penalty shootout.
BVB were without several key player like Pierre-Emerick Aubameyang, Raphael Guerreiro, Schurrle and U.S. international Pulisic, who has enjoyed an excellent season for Borussia so far, scoring two and setting up a further five goals in nine appearances.
On Saturday, Schurrle is set to return to the squad for the first time since scoring the late 2-2 equaliser against Real Madrid in late September, and he will be joined by Pulisic, with the 18-year-old resuming training after an illness earlier this week.
However, Portugal international Guerreiro is likely to miss the match as Tuchel believes the risks outweigh the chances.
Up front, Aubameyang could return following a calf injury, but the Dortmund coach added: "It will be super tight. It's only that his injury cannot worsen when playing. We might grant him a late test on Saturday morning."
Despite leading Schalke by seven points in the Bundesliga standings, Tuchel warned that a defeat could mean that the Royal Blues will be eager to "turn their bad start around" and added that he expects to play a "real men's team."
Both sides meet for the 89th time in Bundesliga. The hosts have won 32 games, drew 26 and lost 30. However, BVB were only able to take four wins from their last 17 home matches against their fierce rivals.
Schalke attacker Klaas-Jan Huntelaar could become the Royal Blues' top scorer in the derby. He has scored five goals, level with four other players. He scored three times against Dortmund, a quarter of his season tally of 12.
Referee Felix Brych will be in charge of his third derby, and in his previous two appearances, both played at the Westfalenstadion, he had no major problems officiating one of the most heated matches in Germany.