For the first time in over three years, Dortmund have lost three games in a row and they go into this home clash with the Serie A side knowing their entire season could depend on its outcome.
Without a win, Dortmund could well be out of the Champions League, or at best, no longer in control of their own destiny, and coming into such a game after a 3-0 defeat to bitter rivals Bayern Munich makes it particularly challenging.
"I've told my players they can be depressed for five minutes, but then things move on," said coach Jurgen Klopp. "We've got to think about our next game.
"This is an unusual situation for us. We just need to draw the right conclusions, add a bit of clarity and then we can be confident about Tuesday."
Dortmund's defensive woes have worsened rather than improved as well.
Although Lukasz Piszczek, after appearing late on against Bayern, could relieve the pressure a little and allow Sven Bender to return to his habitual position in front of the back four, Manuel Friedrich is not registered for the Champions League.
That leaves the inexperienced Koray Gunter or Oliver Kirch to stand in for arguably Dortmund's biggest game of the season.
Napoli, on the other hand, must overcome the absence of captain Marek Hamsik.
The Slovakian midfielder hurt his left foot in Saturday's 1-0 defeat to Parma and will sit out the crucial match in Germany.
Hamsik underwent an MRI scan which ruled out any serious damage but revealed tendinitis in his foot.
"It's unfortunate because he received a knock in the same area where he had been hit before," manager Rafael Benitez said to sscnapoli.it.
Hamsik has joined injured midfielders Juan Zuniga and Giandomenico Mesto on the sidelines.
The Italians go into the encounter at the Westfalenstadion knowing a point will probably suffice. They and Arsenal have nine points and with Dortmund on six, the situation is clear with two games left.
Benitez's men, who beat Borussia 2-1 in Naples back in September, will have to show a vast improvement with respect to their performance against Parma, though.
The loss at the Stadio San Paolo marked Napoli's second straight defeat - their fourth in Serie A this season - and more worryingly for Benitez, for the second game in a row, his team failed to score.
"I am disappointed because we didn't play well," Benitez added. "We didn't play at the level of other games.
"However, I think the teams that compete in the Champions League sometimes can slip and the important thing is we bounce back.
"Now we must focus on our game at Dortmund and try to give our all."