The visitors, meanwhile, have collected just one point from six matches on their travels since gaining promotion.
Match preview
Leipzig have been in poor form on the road themselves in recent times, having lost four of their last five away games in all competitions. As such, head coach Marco Rose and his players may be relieved to be competing at the Red Bull Arena this weekend.
Die Roten Bullen lost away to Wolfsburg for the second time within a month last time out in the Bundesliga, with Jonas Wind and Rogerio scoring either side of half-time for the Wolves. Yussuf Poulsen - who was sent off during his side's defeat to Wolfsburg in the DFB-Pokal in October - had pulled one back seven minutes after the break.
Leipzig looked like pulling off a major upset away to the Champions League holders Manchester City when Lois Openda scored twice before half-time at the Etihad Stadium, but the Citizens pulled off a stunning second half comeback to seal top spot in Group G. Leipzig had already secured their progression to the knockout stages.
Their attentions must now return to picking up their league form, which has become patchier of late. Rose's side have won just three of their last seven matches to slide to fifth in the table, so the former Borussia Dortmund manager will firmly expect his side to secure a win against their newly promoted opponents on Saturday.
However, Heidenheim's only point away from home came against Dortmund, while they almost repeated the trick against the reigning champions Bayern Munich in their last away game. Frank Schmidt's side came from two goals down against the Bavarians before ultimately falling to a 4-2 defeat.
Their most recent match was certainly a far less entertaining one, as they drew 0-0 at home against VfL Bochum. Both sides struggled to create many clear cut chances, with sharing the spoils representing a reasonable outcome as they each looked to move away from the relegation zone.
Indeed, having gained promotion to the Bundesliga for the first time in the club's history, this season was always likely to be a difficult one for Heidenhim. But their tally of 11 points from 12 matches means they head into the weekend's action three points clear of the bottom three.
Given their struggles away from Voith-Arena, Schmidt and his players may not hold too much hope of avoiding defeat at Leipzig, but their excellent performances at other Champions League representatives suggests they should not be completely discounted.
RB Leipzig Bundesliga form:
D
W
W
L
W
L
RB Leipzig form (all competitions):
L
L
W
W
L
L
Heidenheim Bundesliga form:
L
L
L
W
L
D
Heidenheim form (all competitions):
L
L
L
W
L
D
Advert - content below:
Team News
Leipzig will remain without Dani Olmo, Willi Orban and El Chadaille Bitshiabu due to injury, while Timo Werner and Xavi Simons are both unlikely to be risked given their shoulder and groin issues.
Simons was withdrawn after 75 minutes against Man City and is likely to be replaced by Benjamin Sesko from the start on Saturday, allowing Rose to revert to his favoured four-man defensive system after adopting a more counter-attacking approach against the English champions.
Heidenheim, meanwhile, will travel without Elidon Qenaj and Thomas Keller due to knee injuries, while Eren Dinkci is suspended after receiving his fifth caution of the season against Bochum.
Marvin Pieringer and Florian Pick could come into the visitors' starting XI to bolster their attack, but Schmidt is unlikely to make any alterations to his defensive unit after keeping a clean sheet against Bochum.
RB Leipzig possible starting lineup:
Blaswich; Henrichs, Simakan, Lukeba, Raum; Baumgartner, Schlager, Kampl, Forsberg; Openda, Sesko
Heidenheim possible starting lineup:
Muller; Traore, Mainka, Gimber, Fohrenbach; Pick, Maloney, Theuerkauf, Beste; Pieringer, Kleindienst
We say: RB Leipzig 3-1 Heidenheim
Having lost two of their last three league games, Leipzig will be determined to return to winning ways and give themselves a chance of returning to the Champions League qualification spots.
Heidenheim have struggled on the road since gaining their first ever promotion to the Bundesliga, although their excellent efforts at Dortmund and Bayern will give them hope of causing a major upset. We can envisage them scoring but falling to defeat.