Dortmund make the trip to the Veltins Arena facing a four-point gap to leaders Bayern Munich, having suffered a loss to Mainz in their last game on the road and a draw in the subsequent home match against Stuttgart.
Jurgen Klopp's squad has been beset by injuries and Dortmund are yet to keep a clean sheet in the league this season, something that defender Mats Hummels is eager to address.
"We need more stability in defence," said Hummels, who is set to return from a spell on the sidelines against Schalke. "We have already conceded nine goals in five matches which is a very poor record.
"We need to defend better as a team and all 11 players have to play their part. If you concede two goals in each game, as has already happened four times this season, it's very hard to win."
Schalke won 3-0 at Werder Bremen on Tuesday to move out of the relegation zone and will be determined to make it three without a win for their rivals, against whom they have won two and drawn one of their last four clashes.
"It's the biggest derby in Germany," said Schalke coach Jens Keller, who will be without suspended playmaker Julian Draxler. "My players need no motivation."
Champions Bayern Munich head to Cologne still boasting an unbeaten record, but meet a side who have conceded just once in five games - though their two goals scored highlights a pressing problem.
With Mario Gotze, Thomas Muller and Robert Lewandowski starring, Bayern returned to form with a 4-0 thumping of Paderborn on Tuesday, which sent them one point clear of Bayer Leverkusen and Hannover at the summit.
Cologne, on the other hand, have failed to win – or score in – three straight matches, and Bayern's last visit to the RheinEnergieStadion resulted in Muller-inspired 4-1 win.
Elsewhere, Leverkusen and Hannover are away to lowly Freiburg and Stuttgart respectively.
Hoffenheim visit Mainz in a scrap between fourth and fifth in Friday's match - a win for either would take them top - while the following day sixth-placed Borussia Monchengladbach travel to a Paderborn side one spot beneath them and Wolfsburg entertain Werder Bremen in a battle of teams in the bottom half.
Sunday's two games pit Augsburg against Hertha Berlin and rock-bottom Hamburg, who have failed to score in the top flight this season, at home to Eintracht Frankfurt.
