Barcelona target a first trophy under Ronald Koeman in the Spanish Super Cup, while a wobbling Bayern Munich attempt to brush off a shock setback and there are key games at the top in Italy, Portugal and the Netherlands.
AFP Sport selects some of the standout football action in Europe this weekend:
Spanish Super Cup final
Barcelona v Real Madrid, Sunday 2000 GMT
Lionel Messi is expected to return for Sunday's Spanish Super Cup final against Athletic Bilbao, who defeated Real Madrid to set up a second meeting between the clubs in as many weeks following Barcelona's 3-2 victory in La Liga on January 6.
As Atletico Madrid threaten to streak clear in the league, Barca face a daunting task in reviving their title hopes but are improving under Koeman, unbeaten in nine games and with a trophy in their grasp.
This is the second year of the competition's new format, which has four teams playing each other in a semi-final and final.
Last season's version, won by Real, controversially took place in Saudi Arabia, but the pandemic means this year's semis were in Cordoba and Malaga, with the final to be played in Seville.
In-form Freiburg await creaking Bayern
Bayern Munich v Freiburg, Sunday 1430 GMT
Following a dream first season at the helm, Bayern Munich coach Hansi Flick is finally going through a testing patch in Bavaria after back-to-back failures.
Bayern threw away a two-goal lead in a 3-2 loss at Borussia Moenchengladbach last week, the latest in a line of worrying defensive displays, and then crashed out of the German Cup to second-tier Holstein Kiel on penalties.
Their second-round exit represented Bayern's earliest in the competition for 20 years, and squashed aspirations of repeating last season's remarkable treble.
While they remain two points clear at the top of the Bundesliga, Bayern could again be exposed by a Freiburg side on a five-match winning run and brimming with confidence.
Sharpshooters collide in Derby d'Italia
Inter v Juventus, Sunday 1945 GMT
After inflicting a first defeat on AC Milan this season, fourth-placed Juventus face a key stretch in their pursuit of a 10th consecutive Serie A title with games against Roma and Napoli on the horizon following their trip to Inter.
Juve, who like both Inter and Milan needed extra time to reach the Italian Cup quarter-finals this week, finished just a point above Antonio Conte's side last term and are unbeaten in seven against the Nerazzurri.
Inter have dropped points in successive weeks following an eight-match winning run, but will hope Romelu Lukaku can add to his 12 goals in a clash against Cristiano Ronaldo, the league's leading scorer (15).
Clash of Portuguese giants
Porto v Benfica, Friday 2100 GMT
Portugal's two most successful clubs know the importance of their showdown at the Estadio do Dragao, as Porto host Benfica with both sides trailing unbeaten league leaders Sporting Lisbon by four points.
With a combined 66 titles between them, Porto and Benfica have long dominated the top-flight but Sporting are threatening to halt their 18-year hegemony this season under ex-Benfica player Ruben Amorim.
After a rocky start defending champions Porto have won seven in a row, while Benfica have an identical record 13 games in and are unbeaten in six. Both however could find themselves seven points behind Sporting at kick-off, with Rio Ave visiting the capital earlier on Friday.
De Klassieker evokes distant memories
Ajax v Feyenoord, Sunday 1545 GMT
Sworn enemies Ajax and Feyenoord go head to head in Amsterdam in the Dutch Eredivisie this weekend, a clash which stirs memories of a rivalry that peaked in the mid-1970s -- at home and on the continent.
The Netherlands was represented by one of the two teams in each of the five European Cup finals between 1969 and 1973 in a golden age for Dutch football.
Feyenoord, under the tutelage of Austrian boss Ernst Happel, won the country's first European title in 1970 before Ajax, spurred on by the success of their foes, reeled off three straight victories adhering to the "Total Football" philosophy preached by coach Rinus Michels and exemplified by Johan Cruyff.