Last season's Champions League runners-up Dortmund go into the game on the back of a 2-1 win at Arsenal that put them firmly on track for a top-two group finish.
However, with two wins in their last four Bundesliga games, the 2011 and 2012 Champions have dropped one point behind leaders Bayern Munich after briefly losing their domestic focus.
The match against Schalke is the highlight for all Dortmund fans and victory would only strengthen their confidence about challenging Bayern for domestic glory.
Dortmund won the league in 2011 and 2012 but lost out to treble-winning Bayern last season.
"It is easier to recover after winning a game, especially mentally and that will help us a lot in the derby," said Dortmund midfielder Henrikh Mkhitaryan.
"I was told early on what kind of importance that game has and I am really looking forward to it," added the Armenian, who was on target against Arsenal.
Schalke, on the other hand, will want to wipe the slate clean after a 3-0 defeat to visiting Chelsea in their own Champions League match on Tuesday.
"We do not need to be motivated for such a game. The Bundesliga derby starts from 0-0 and it will be a fiercely-contested game," said Schalke goalkeeper Timo Hildebrand. "Dortmund will not be defending like Chelsea and we have learned our lessons from that game."
Schalke will be without injured Jefferson Farfan and Marco Hoeger as well as long-term absentees Klaas-Jan Huntelaar and Kyriakos Papadopoulos.
There is also a big question mark over the fitness of Kevin-Prince Boateng, who recovered from a two-week knee injury break in time for Chelsea but was a long way from his best.
He played in an unusual forward position against Chelsea but made no impact.
"I played him as a forward because he did not need to run that much in that position," said Keller. "He has hardly trained in two weeks and told me at halftime he had run out of steam."
Bayern Munich entertain promoted Hertha Berlin while third-placed Bayer Leverkusen, level with Dortmund on 22 points, host Augsburg (both 1330).