Leverkusen find themselves a point behind Bayern Munich, who they held to a 1-1 draw last time out, and level on points with Borussia Dortmund, who were beaten by fourth-placed Borussia Monchengladbach.
In spite of that first defeat of the season, Dortmund are still six points clear of Gladbach and Hannover.
Dortmund host Hannover on Saturday while Bayern face a Mainz side who have picked up just a single point from their past five games, and Leverkusen can steal a march on both with victory over Hoffenheim as a gulf begins to appear in the German game.
Werder Bremen used to find themselves among the frequent frontrunners, but in this, their third season without European football, their coach Robin Dutt fears that gulf is only going to get wider.
"If you consider the next 10 years, then you're probably not going to get anywhere near to Leverkusen, Schalke, Dortmund and Bayern," he told the Weser Kurier.
"We've got to invest in our own youth and we've got to have the aim of ensuring the fans see, in 13 or 14 of our 17 home games, the kind of football which leaves them feeling it's fantastic to pay the Weserstadion a visit."
That is precisely what he will be hoping to deliver against his former club Freiburg on Saturday with a place in the top five beckoning, in spite of Dutt's caution.
Freiburg head to Bremen in search of their first win of the season with Nurnberg also after their first triumph at Eintracht Frankfurt, although Eintracht Braunschweig are now off the mark thanks to a 2-0 win at Wolfsburg and they will be looking to celebrate at home to Schalke this Saturday.
On Saturday evening, Gladbach travel to Hertha Berlin with both home and away coach, Jos Luhukay and Lucien Favre respectively, meeting former clubs, while Sunday's games see Hamburg and Stuttgart, the only two sides to have changed coaches so far this season, meet at the HSV-Arena and Augsburg entertain Wolfsburg.