Manchester United travel to historic rivals Leeds on Sunday with pressure mounting on manager Michael Carrick, while Manchester City aim to extend their perfect Premier League start despite uncertainty over their future.
Brighton could be one of the big winners should City suffer severe sanctions for breaking financial rules.
The Seagulls are riding high, just two points behind second-placed Arsenal, ahead of their grudge match against Crystal Palace.
AFP Sport looks at the pick of the action from the English top flight this weekend.
MAN UTD'S WORST START IN 40 YEARS
United are off to their worst league start in 40 years and were plunged further into chaos by defender Lisandro Martinez's attack on the club's hierarchy over a lack of investment in the squad after Tuesday's 2-0 defeat by Atletico Madrid.
The Argentine took aim at technical director Jason Wilcox after the Red Devils' main transfer business during the summer window focused on bringing in three midfielders.
But Martinez himself has been one of those most culpable for a miserable start to the campaign for his part in goals conceded to Fulham and Tottenham in recent weeks.
United have won just one of their opening six league games and were also dumped out of the League Cup by Brighton.
Leeds last beat the Red Devils at Elland Road back in 2002, but did inflict the only home defeat of Carrick's interim spell in charge last season when the sides met in April.
Carrick is under increasing pressure as the latest manager struggling to reverse a sharp decline at Old Trafford since Alex Ferguson's retirement in 2013.
But he said the hostile atmosphere his side will face in Leeds gives United the perfect chance to bounce back.
"What a great game (on) Sunday to prepare for. It's a fantastic game for us, for the club, for the history, for the supporters," said Carrick.
"Everything to do with the game is a great game so we'll be ready for that."
CITY CASE LEAVES LEAGUE IN LIMBO
Manchester City sit pretty at the top of the table with six wins from six league games, but that could all count for nothing if they do not successfully overturn a guilty verdict on more than 100 charges of breaking Premier League rules.
Enzo Maresca's men shut out that distraction to win 3-0 at Liverpool last weekend and rallied impressively in the second half despite losing 4-2 to Paris Saint-Germain in a thrilling Champions League tie on Tuesday.
But the uncertainty over their future has left the entire league in limbo.
City deny any wrongdoing and the long-running case still has at least a few months left to run before the appeal process concludes and potential sanctions are announced.
"My underlying thought is none of this is good for football and there are no winners," said former England manager Gareth Southgate.
City can stretch their lead at the top to six points when Ipswich visit the Etihad on Saturday, with Arsenal not in action until 24 hours later at Nottingham Forest.
'RUTHLESS' BRIGHTON EYE CHAMPIONS LEAGUE
Arsenal's only defeat this season came in a 3-0 trouncing by Brighton, who could reach new heights this season with a clutch of the established giants struggling.
Brighton have soared through the divisions and into Europe on the back of owner Tony Bloom's expertise in data analytics.
But they are yet to play Champions League football.
Despite routinely selling their prized assets to wealthier clubs, Brighton's smart recruitment of both players and coaches has ensured they have continued to thrive.
That has also made them popular among neutrals, but manager Fabian Hurzeler wants his side to show their nasty side against rivals Palace on Sunday.
"We want to be ruthless. We want to create this energetic atmosphere where it makes it so hard to come to this place," said Hurzeler. "We have to keep building this together with our fans and not be the nice football club anymore."
Fixtures
Saturday
Everton v Chelsea (1:30pm), Fulham v Hull, Brentford v Liverpool, Manchester City v Ipswich (all 4pm), Newcastle v Aston Villa (6:30pm)
Sunday
Brighton v Crystal Palace, Leeds v Manchester United, Bournemouth v Sunderland (all 3pm), Nottingham Forest v Arsenal (5:30pm)
Monday
Tottenham v Coventry (9pm)