Dortmund, who cut the gap to two points with a 1-0 victory at Bayern last weekend, will be without holding midfielder Sven Bender after he broke his jaw in the 2-1 defeat by Arsenal in the Champions League on Wednesday.
Playmaker Mario Gotze could also miss the meeting of the Ruhr valley rivals after picking up a knock just above the knee against Arsenal.
"Dortmund will be without Bender until January," the club said on Thursday after the 22-year-old underwent a three-hour operation in London.
"Gotze's derby participation is also in doubt [but] the medical staff are hoping he can be fit for Saturday."
Germany international Gotze has led Dortmund's recent revival and scored the winning goal against Bayern.
The champions are already without central defender Never Subotic who is recovering from a broken cheekbone.
The injuries could not have come at a worse time for Dortmund, who have recovered from a bad start by winning six of their last seven league games to move up to second spot. Schalke are a point behind in fourth.
"Beating Dortmund would be a major boost for us," said Schalke midfielder Lewis Holtby. "They played well in Munich last week but the mother of all derbys in Germany is a different story."
Bayern, who defeated Villarreal 3-1 in the Champions League on Tuesday to book their spot in the next round, travel to lowly Mainz on Sunday.
Third-placed Borussia Monchengladbach, level on 26 points with Dortmund, travel to Cologne on Friday.
