Promoted Sunderland, who have defied expectations to stay in the top half of the Premier League table, could be the worst affected with six players going to the tournament, while the likes of Fulham, Manchester United, Burnley and Crystal Palace will also have to make do without some key personnel.
Ajax Amsterdam produced a performance worthy of the club's illustrious past when they crushed Olympique Lyonnais 4-1 on Wednesday to move to the brink of their first European final since 1996.
Midfielder Phil Foden delivered in dramatic fashion, scoring in the first and 91st minutes, to seal Manchester City's 3-2 victory over Leeds United.
Paris St Germain completed a domestic treble as they beat Olympique Lyonnais 6-5 on penalties to lift the French League Cup on Friday with the match ending in a 0-0 stalemate after regular and extra time. Second-half substitute Pablo Sarabia scored PSG's final penalty in the shootout after goalkeeper Keylor Navas had saved Bertrand Traore's spot kick to give the Ligue 1 champions and French Cup winners their ninth League Cup trophy.
Forward Rasmus Hojlund scored twice to allow Manchester United to come back from a goal down and get a 2-1 win at six-times Czech champions Viktoria Plzen in the Europa League on Thursday.
Images from Tuesday's action in the Premier League
The win leaves United in 15th place in the Europa League standings on six points from four games.
Photos from the English Premier League matches played on Saturday
News of all that's transpired on and off the football field
Chelsea captain John Terry is showing all the qualities of a future manager, the club's interim boss Guus Hiddink said on Friday. Terry, 35, is keen to continue his playing career at Stamford Bridge but has not yet been offered a new contract for next season. Hiddink said decision was not down to him, but in the longer term he could see the former England central defender as a manager. "In some players you see while they are playing there might be managers inside them already," the Dutchman told a news conference. "You see that most of the time in midfield positions or centre-backs. These guys are already leaders. "In my career I've had some examples like (Southampton's) Ronald Koeman in my first spell at Eindhoven, who you could see was tactically very strong and a leader. "And (Watford's) Quique Sanchez Flores at Valencia too." Terry would need "extra courses" and would be well advised to start as an assistant, Hiddink added.
Chelsea finally produced a performance befitting of champions to demolish Newcastle United 5-1.
Chelsea banished any fears of a repeat of last season's shock FA Cup fourth-round exit to Bradford City when they crushed Championship (second-tier) side Milton Keynes Dons 5-1 away to reach the fifth round on Sunday.
News of all that's transpired on and off the football field
Manchester United closed in on the Premier League's pole position after a 2-1 home win over Aston Villa on Friday put them level on points and games played with champions and leaders Liverpool.
News of all that's transpired on and off the football field
Manchester City chalked up yet another victory to maintain their stranglehold of the Premier League title race but pursuers Manchester United and Leicester City both secured important wins to enhance their top-four bids on Sunday.
Ronaldo's replacement Dybala scored in the 77th minute with a goal the Portuguese would have been proud of. After a quick exchange of passes, the Argentine twisted past Alessio Romagnoli and beat Gianluigi Donnarumma with a right foot shot.
Troubled AC Milan were held to a goalless draw by AEK Athens
Arsenal ended their seven match winless run in the Premier League with a surprise 3-1 London derby victory over Chelsea at the Emirates Stadium on Saturday while Manchester United were held to a 2-2 draw at Leicester City.
Ole Gunnar Solskjaer's side, who had won their last ten away games in the Premier League, stay third on 27 points, a point behind second-placed Leicester.
Roberto Firmino scored twice and Marquinhos and Philippe Coutinho also got goals as Brazil hammered Bolivia 5-0 in their opening World Cup qualifier in Sao Paulo on Friday.
A summary of Thursday's matches in Europe's second tier club football tournament
Schalke 04 hit back from two goals down to draw 2-2 and overcome fellow Germans Borussia Moenchenglach on away goals in their Europa League last 16 tie while Manchester United edged Rostov 1-0 to progress on Thursday.
Inter Milan's aversion to Europa League football continued with a 3-1 defeat at Sparta Prague, while AS Roma ended a continental hoodoo stretching back seven games with a 4-0 home win over Romanian side FC Astra on Thursday.
Former Real youth player Joselu pulled a goal back for Alaves in the 59th minute, powering in a header from a free kick, but Benzema rounded off the victory for second-placed Real with an exquisite solo run and goal in the 70th minute.
News of all that's transpired on and off the football field
Chelsea exploited Manchester City's decision to field a weakened team by romping to a 5-1 win in the FA Cup fifth round on Sunday as they joined London rivals West Ham United and Crystal Palace in the quarter-finals.
IMAGES from the English Premier League matches played on Saturday
Chelsea's third successive league win lifted them level on 18 points with Leicester City but are top thanks to a better goal difference. Leicester face Liverpool on Sunday.
La Liga leaders Barcelona handed Real Madrid more hope in the title race as they drew 0-0 at Athletic Bilbao on Sunday, only avoiding defeat thanks to some outstanding saves by Marc-Andre ter Stegen.
A summary of Tuesday's Group stage matches in the UEFA Champions League.
Images from English Premier League matches played on Sunday.
David de Gea's late own goal earned Sunderland a 2-1 win over Manchester United on Saturday and a vital three points in their bid for Premier League survival.
Juventus raced into a 2-0 halftime lead after Napoli goalkeeper Alex Meret was sent off in the 25th minute. The visitors then had Pjanic dismissed and Napoli's Jose Callejon pulled one back before Insigne let the Turin side off the hook.
Brighton and Hove Albion scored late to earn a 1-1 draw at Crystal Palace. Sheffield United and Fulham also drew 1-1 as both teams picked up their first points.
News of all that's transpired on and off the football field
News of all that's transpired on and off the football field
Images from the EPL matches played on Sunday
Everton have been handed the dubious distinction of being the 'dirtiest' Premier League team after a study on the all-time cards and fouls by www.dirtyteams.co.uk.
IMAGES from Saturday's English Premier League matches.
