The hosts have to win in order to keep their hopes of making the last 16 alive, but a draw will do for Rafa Benitez's men.
Die Schwarzgelben has lost three matches in a row – something that has not happened since February 2010 – and has slipped to third in the Bundesliga as a result.
A 1-0 home defeat to Arsenal in Group F was followed by domestic defeats to Wolfsburg and Bayern Munich, leaving Jurgen Klopp's men off the pace in the German top flight and at risk of missing out on the last 16 in Europe's premier club competition.
Club captain Sebastian Kehl (ankle) and defender Lukasz Piszczek (hip and groin) made the bench against Bayern but Dortmund continues to be plagued by injuries to key players.
First-choice center back pairing Neven Subotic and Mats Hummels are long-term absentees, while left-back Marcel Schmelzer (calf) and midfielder Ilkay Gundogan (back) are also currently unavailable.
Subotic is likely to miss the rest of the season after suffering knee ligament damage at Wolfsburg, while Hummels tore ligaments in his right heel when on international duty with Germany.
As a result, Klopp moved for free agent Manuel Friedrich, a former Germany international who left Bayer Leverkusen at the end of last season and made his debut in Saturday's loss to Bayern.
Dortmund – which sits third in Group F with two wins from four matches – will hope Robert Lewandowski breaks a five-match goal drought for club and country against Rafael Benitez's men.
The previous encounter between the two sides saw Napoli post a 2-1 home win thanks to strikes from Gonzalo Higuain and Lorenzo Insigne.
Successive Champions League triumphs against Marseille have Napoli well placed to reach the round of 16, with nine points from its four matches.
It needs just a draw in Germany to qualify from the group but heads into the game on the back of two Serie A defeats on the bounce.
Marek Hamsik moved to equal fifth on the club's all-time appearances list after coming off the bench in Saturday's 1-0 home loss to Parma, but he limped off just nine minutes later with a foot injury that rules him out of this encounter.
Defenders Camilo Zuniga and Giandomenico Mesto will also be sidelined for the visitors with knee injuries.