Bremen, who narrowly avoided relegation last season, will be looking to gain revenge on their opponents having lost both meetings last season.
Florian Kohfeldt's side look much improved on last season having taken seven points from their last three matches, with Niclas Fullkrug's fourth goal in as many matches earning Bremen a point at Freiburg last weekend.
The 27-year-old striker missed almost the entirety of last season after rupturing his cruciate ligament only a few weeks after signing from Hannover, which was a major factor for Bremen having to endure the nightmare of Germany's relegation playoff at the end of last season.
Bremen preserved their top flight status, which impressively stretches all the way back to 1981, by the skin of their teeth after drawing 2-2 to Heidenheim across two legs. Away goal deciders are not everyone's cup of tea in football, but it is certainly popular in Bremen for the foreseeable future.
With Leonardo Bittencourt in top form so far this season, winning the penalty which Fullkrug converted at Freiburg, Die Werderaner fans can be hopeful of a much better showing this time around after a positive start.
Hoffenheim, meanwhile, shocked the world with a 4-1 win against Bayern Munich earlier in the campaign, but without star striker Andrej Kramaric - forced to quarantine due to coronavirus since the international break - they could not repeat their magic when falling 1-0 at home to Borussia Dortmund at the weekend.
Mijat Gacinovic should have opened the scoring for the hosts in the opening exchanges, missing on the stretch from eight yards after a fine cross from Robert Skov, but Dortmund dominated the rest of the match and were deserved winners.
Sebastian Hoeness will have been encouraged by his side's 2-0 win against Red Star Belgrade in the Europa League in midweek, though, in what is only the club's third European campaign. With Gent and Slovan Liberec the other sides in Group L, Die Kraichgauer can be hopeful of topping the group.
Munas Dabbur scored late in the match to seal the three points, and Hoeness will need him in top form until Kramaric's return in order to avoid a third consecutive league defeat.
Werder Bremen Bundesliga form: LWWD
Werder Bremen form (all competitions): WLWWD
Hoffenheim Bundesliga form: WWLL
Hoffenheim form (all competitions): WWWLLW
Having missed the first three games of the new season with a knee problem, Bremen's top goalscorer in the last two campaigns Milot Rashica played 24 minutes in the draw with Freiburg and could earn his first start of the season if Kohfeldt deems him fit enough.
With Ludwig Augustinsson out with a thigh strain, the Bremen boss could revert to a back four in order to accommodate Rashica into the starting XI. Felix Agu and Tahith Chong are unavailable due to coronavirus, with Patrick Erras out with a hamstring strain.
Kramaric is one of three Hoffenheim players currently quarantining due to coronavirus, with Kasim Adams and Pavel Kaderabek also unavailable. Ermin Bicakcic and Kostas Stafylidis are out through injury.
After scoring in midweek, Dabbur should return to the starting lineup alongside Christoph Baumgartner, with both only used as substitutes in the defeat to Dortmund.
Werder Bremen possible starting lineup:
Pavienka; Gebre-Selassie, Veljkovic, Moisander, Friedl; Eggestein, Mborn, Bittencourt; Sargent, Fullkrug, Rashica
Hoffenheim possible starting lineup:
Baumann; Posch, Vogt, Akpoguma; Rudy, Samassekou, Geiger, Skov; Baumgartner, Dabbur, Belfodil
We say: Werder Bremen 2-1 Hoffenheim
With Hoffenheim playing in Europe in midweek, Bremen will be the fresher of the two sides and are also in better form with fewer players missing. As such, we think they may have enough to earn a win against a side who look vulnerable without the excellence of Kramaric in attack.