Manchester City are set for a hostile reception at Liverpool on Sunday in their first outing since being found guilty of over 100 breaches of Premier League financial rules.
City have appealed and proclaim their innocence, but the Premier League leaders' place in the division is now under threat following findings that they used "sham" sponsorship deals to inflate revenues and reduce costs by more than £900 million ($1.2 billion).
Manchester United and Tottenham are both badly in need of a win when they meet at Old Trafford, while Arsenal aim to bounce back at home to Leeds following a rare defeat.
We look at the pick of the action as the English top-flight returns after a three-week international break.
CITY FACE THE MUSIC
City's transformation into the dominant force in English football since an Abu Dhabi-backed takeover 18 years ago has cost Liverpool more than most.
The charges labelled against City cover the period between 2009 and 2018, but the foundations they built in that time ensured they remained the Premier League's top dogs during the bulk of Pep Guardiola's subsequent time in charge.
Jurgen Klopp's Liverpool twice missed out on the title to Guardiola's side despite amassing over 90 points.
Those battles to be crowned champions of England over the past decade have turned this fixture into the Premier League's marquee match-up and the eyes of the football world will be on Anfield again come Sunday.
City have won every game since Enzo Maresca replaced Guardiola, but their title challenge is likely to be ruined by a sanction unless they can overturn the verdict of an independent commission.
Liverpool will seek to capitalise on City's uncertainty and kickstart their own campaign.
Andoni Iraola remains unbeaten as Liverpool manager, but draws against Newcastle, Nottingham Forest and Fulham have left the Reds six points off top spot.
"I think it's a big game and I think everyone is expecting to play, to watch, to be part of that game," said Iraola.
"We know we will have to be at our best and also I know that the people will be looking to help the team."
PRESSURE ON CARRICK
City's scandal took the attention away from a difficult start to the season on the other side of Manchester.
United have taken just five points from what appeared an inviting opening five fixtures and now face a difficult run.
Just months after being handed the job as manager on a permanent basis, Michael Carrick is the latest United boss facing scrutiny over his ability to turn around the fortunes of the ailing English giants.
After Saturday's visit of Spurs, the Red Devils travel to Atletico Madrid, Leeds and Como in a nine-day period and also face Chelsea, Roma and Aston Villa before next month's international break.
Tottenham spent over £300 million on new players during the transfer window, but still had to endure the past three weeks rooted to the foot of the table after taking just two points from their opening five games.
ARSENAL JUST GETTING STARTED
Defending champions Arsenal are aiming to strike back when Leeds visit the Emirates in Saturday's early kick-off.
A perfect start to the campaign for the Gunners ended in dramatic fashion with a 3-0 defeat at Brighton in their last outing.
But developments in the City case have reinforced Mikel Arteta's men as bookies' favourites to retain the title.
Arsenal manager Arteta extended his contract till 2030 this week and is determined that a first league title in 22 years is only the beginning of a golden age for the north London club.
"This is only the beginning of what we can achieve together," said the Spaniard.
Fixtures (all times CAT)
Saturday
Arsenal v Leeds (13:30), Aston Villa v Brentford, Chelsea v Bournemouth, Ipswich v Fulham, Sunderland v Brighton (all 16:00), Manchester United v Tottenham (18:30)
Sunday
Crystal Palace v Nottingham Forest, Hull v Everton (both 15:00), Liverpool v Manchester City (17:30)
Monday
Coventry v Newcastle (21:00)