The sides meet at the Coface Arena and it is the hosts who are in better domestic form, having won three of their last four top-flight games, with Shinji Okazaki finding the net on four occasions in that time.
However, Mainz have not beaten Saturday's opponents in their last six attempts, as Jurgen Klopp returns to a club where he both played and managed.
Klopp's Dortmund have stalled somewhat in the Bundesliga recently, losing 2-1 at Wolfsburg prior to the international break before going down 3-0 at home to champions Bayern Munich last time out.
Despite injuries to the likes of Marcel Schmelzer, Mats Hummels and Neven Subotic, Dortmund kept their hopes of UEFA Champions League qualification alive on Tuesday with a 3-1 win over Napoli.
Sven Bender sustained a broken nose in that match but was able to finish the game, although Klopp is keen to leave any decisions on selection until as late as possible.
"We still have two days to make a decision," Klopp said.
"We will look carefully to know who can cope with the burden (of playing twice in five days). We will deal with the issue of rotation and look for who is fit."
Klopp signed Manuel Friedrich in an attempt to bolster his depleted defence and revealed his pleasure at how the 34-year-old has fitted in at Signal Iduna Park.
"Manny embodies all that makes up our game and what we have shown in recent years," he said. "He has an exceptional character."
Dortmund have dropped points in half of their Bundesliga matches on the road this season, while Mainz have not lost at home in their last three.
Their last two matches in Mainz have yielded 2-0 and 1-0 wins over Eintracht Braunschweig and Eintracht Frankfurt respectively, while they were 3-2 winners over Werder Bremen at the Weserstadion on Sunday.
Mainz coach Thomas Tuchel has also been handed a boost with the news that Zdenek Pospech is fit despite being taken off in the win over Bremen, while Christian Wetklo is available for a return after serving his suspension.
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