A resurgent AC Milan are looking to reclaim local bragging rights, while Hoffenheim target another big scalp in the Bundesliga and an awkward assignment awaits Barcelona.
AFP Sport picks out some of the standout action in Europe this weekend:
Can Hoffenheim do it again?
Hoffenheim v Borussia Dortmund, Saturday 15:30
Hoffenheim made headlines last month when they beat Bayern Munich 4-1. On Saturday the side coached by ex-Bayern reserve boss Sebastian Hoeness are looking to get the better of Borussia Dortmund.
Both sides have taken six points from their first three games, and this match brings together two of the hottest strikers in Europe.
Erling Braut Haaland has been a sensation for Dortmund and scored twice in their 4-0 win over Freiburg last time out. But the Bundesliga's top scorer is Hoffenheim's Andrej Kramaric with six goals, plus two more in the German Cup.
Kramaric, who was in goal-scoring form for Croatia over the international break, netted all the goals when Hoffenheim won 4-0 in Dortmund on the final day of last season.
Milan confident ahead of derby
Inter v AC Milan, Saturday 18:00
AC Milan have not beaten Inter in Serie A in eight attempts since a 3-0 victory in January 2016. They have lost their last four meetings and have only finished above their local rivals once in seven years.
But there is belief among the Rossoneri that the tide might be turning in Milan ahead of Saturday's "Derby della Madonnina".
Antonio Conte's Inter pushed Juventus closer than anyone else last season and have started this campaign with seven points out of nine. However, Milan have won three out of three to sit joint-top with Atalanta. On Saturday they will have Zlatan Ibrahimovic back after coronavirus.
"The gap with Inter has been reduced, because the club did well in the transfer market, although Inter have also strengthened," Milan goalkeeper Gianluigi Donnarumma told Sky Italia.
"(Coach Stefano) Pioli is doing great things and now we need to go out on the field and show that the gap has been reduced."
Napoli aim to bounce back
Napoli v Atalanta, Saturday 15:00
Gennaro Gattuso's Napoli are hoping to get back on track after their aborted trip to Juventus before the international break.
They did not turn up for the game in Turin after two positive coronavirus cases, instead remaining in isolation on the instructions of local health authorities.
As a result they were handed a 3-0 defeat and docked a point, a setback for a side who won their first two game this season.
They could not have asked for a tougher test this weekend, however, as Atalanta head to the San Paolo fresh from winning their first three games and scoring 13 goals.
Messi to be rested?
Getafe v Barcelona, Saturday 21:00
After helping Argentina to a World Cup qualifying win in Bolivia, and ahead of Barcelona's Champions League opener against Ferencvaros, Lionel Messi could start on the bench at Getafe in La Liga.
The game will be an awkward one for Ronald Koeman's side, who have taken seven points from a possible nine in La Liga and host Real Madrid in the first Clasico of the campaign next weekend.
Madrid are already three points ahead of Barca, albeit having played a game more, and they appear to have a more straightforward assignment this weekend against Cadiz.
Sporting v Porto, Saturday 21:30
The first 'Classico' of the Portuguese season goes ahead in Lisbon on Saturday when Sporting host champions Porto, and the biggest winners could be Benfica.
It is the latter who top the early table, with their two great rivals both three points behind.
Sporting may be the club where the likes of Cristiano Ronaldo and Bruno Fernandes once starred, but they have not won the title since 2002 and have not beaten Porto in over four years.
They may stand a chance here, though, if Porto - who sold full-back Alex Telles to Manchester United just before the transfer deadline - have their focus diverted towards their upcoming Champions League clash with Manchester City.