Hoffenheim won both meetings between the two sides without conceding a goal last campaign, so will be viewing this match as an opportunity to get back to winning ways.
Indeed, Sebastian Hoeness's side have taken only one point from their last three matches since stunning the world by beating European champions Bayern Munich 4-1 prior to the international break.
A major factor for their downturn in form has undoubtedly been the absence of Andrej Kramaric, who tested positive for coronavirus during the break, but the Croatian striker is back in contention to return to the team against Union Berlin.
Hoffenheim were unfortunate not to beat Werder Bremen when drawing 1-1 last weekend, with Die Kraichgauer having the better of the match once Dennis Geiger had equalised with a superbly-placed finish into the top corner.
Hoeness's side did at least make it two wins from two in the Europa League, though, with a terrific 4-1 victory at Belgian side Gent on Thursday. Ishak Belfodil and Munas Dabbur both scored in Kramaric's absence, with Hoffenheim having an incredible 33 shots, with 15 of them testing the opposition goalkeeper.
Union Berlin, who are competing in the Bundesliga for only the second season in the club's history having survived in their debut campaign, were also unfortunate not to win in a 1-1 draw with Freiburg last weekend.
Vincenzo Grifo had given the visitors the lead against the run of play with a tremendous curling finish from the left side of the penalty area, before fine work from Max Kruse against his former club teed up Robert Andrich to equalise with a deflected effort from distance.
Urs Fischer's side pushed for a winner and should have had it when Marvin Freidrich narrowly headed wide from close range with only a matter of minutes remaining on the clock. The defender already has two goals to his name this season, but the anguish on his face was clear as he knew a third would have secured an invaluable three points for his side.
Fischer will be content that his side remain unbeaten since the opening day, however, with the 4-0 win against Mainz 05 sandwiched by three 1-1 draws either side of it. Another draw at a Hoffenheim side who will be expected to compete in the top half of the table would not necessarily be a bad result, especially if the dangerous Kramaric starts.
Hoffenheim Bundesliga form: WWLLD
Hoffenheim form (all competitions): WLLWDW
Union Berlin Bundesliga form: LDWDD
Union Berlin form (all competitions): WLDWDD
Kramaric has not played for a month, but should be thrown into the starting XI in place of Jacob Bruun Larsen, with Hoffenheim desperately missing the Croatian's pace and goal threat in recent weeks.
Last weekend's goalscorer Geiger is unlikely to feature due to knee problems, with Benjamin Hubner (joint tear), Kostas Stafylidis (shoulder), Ermin Bicakcic (cruciate ligament rupture) all long-term absentees.
For Union Berlin, former Liverpool goalkeeper Loris Karius may be fit to make his debut for the club having made good progress with his foot injury, but he may have to wait to make his first Bundesliga appearance since May 2016 with Andreas Luthe in decent form between the sticks.
Hoffenheim possible starting lineup:
Pentke; Posch, Vogt, Akpoguma; Rudy, Gacinovic, Samassekou, Skov; Baumgartner, Dabbur; Kramaric
Union Berlin possible starting lineup:
Luthe; Trimmel, Friedrich, Knoche, Lenz; Andrich, Gentner; Becker, Kruse, Ingvartsen; Pohjanpalo
We say: Hoffenheim 2-1 Union Berlin
Should Kramatic be deemed ready to start by Hoeness, he clearly increases Hoffenheim's chances of winning this match by a considerable amount against a side they got the better of in both meetings last season.
However, Union Berlin will be no pushovers either way, as they showed when claiming a surprise point at Borussia Monchengladbach a few weeks ago.