Liverpool's faltering Premier League title challenge could suffer a fatal blow if leaders Arsenal win Sunday's marquee match-up at the Emirates Stadium.
Powered by Erling Haaland's incredible form, Manchester City will aim for another goal spree against Southampton, while Manchester United could turn to Brazilian midfielder Casemiro after their derby demolition.
AFP Sport looks at some of the key talking points ahead of this weekend's action.
Liverpool face defining period
Virgil van Dijk has urged Liverpool to embrace the pressure of a potentially defining period in their stop-start season.
Hampered by an unusually sluggish start, Jurgen Klopp's side are already 11 points behind Arsenal and can ill-afford to fall further adrift.
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Winners of just two of their first seven league games, Liverpool follow that crucial clash in London with a Champions League trip to Rangers on Wednesday before Manchester City visit Anfield on October 16.
After a damaging 3-3 draw with Brighton last weekend, Liverpool recovered their equilibrium by beating Rangers 2-0 in midweek and Van Dijk wants his team to take that momentum into the Arsenal game.
"It's something to look forward to. They (Arsenal) are in a fantastic moment but if you look at our results in the Premier League I think no one would give us a chance there," said defender Van Dijk.
"But we know what we are capable of, we know what is expected. They are in the best moment of their lives, full of confidence, and it's a big game."
Lasagne fuels Haaland's hot streak
As defenders across Europe struggle to sate Erling Haaland's appetite for goals, the Manchester City striker has revealed his recipe for success.
Haaland is in such prolific form that he was only needed for the first half of City's 5-0 rout of Copenhagen in the Champions League on Wednesday, during which he netted twice.
The 22-year-old has scored 19 goals in 11 competitive games in a remarkable first season with City following his £51 million ($57 million) move from Borussia Dortmund.
And the Norway star says his dad Alfie's home-cooked lasagne has played a key role in his blistering run.
"I've had it before every home game now and that turns out fairly well, so there has to be something special he adds to it," said Haaland.
"I help out very little. I mostly lie on the couch watching him. That's the way it works."
With Haaland adding the attacking fulcrum City had lacked since Sergio Aguero's departure, the champions have embarked on a power surge featuring 29 goals in their first eight league games.
No wonder City boss Pep Guardiola was quick to deny reports in Spain this week that Haaland's City contract contains a clause that allows Real Madrid to sign him from 2024.
Ten Hag wrestles with Casemiro dilemma
Erik ten Hag could finally give Brazil midfielder Casemiro his first Premier League start as the Manchester United manager tries to steady his side after their "reality check" at Manchester City.
United's four-match winning league run came to a painful end when City hammered them 6-3 last weekend.
Ten Hag believes that chastening defeat should serve to refocus his players for Sunday's trip to Everton, but he has a significant selection dilemma to solve first.
Since signing Casemiro from Real Madrid for an initial £60 million in August, Ten Hag has used the five-time Champions League winner sparingly due to Scott McTominay's solid performances.
Casemiro has made four substitute appearances in the Premier League, with his only starts coming in the Europa League, but the derby meltdown could be the trigger for a sustained promotion to the starting line-up.
"I said already before, it had nothing to do with Casemiro, it was all to do with Scott," said Ten Hag. "I'm sure Casemiro will play a really important role."
Saturday (1400 GMT unless stated)
Bournemouth v Leicester, Chelsea v Wolves, Manchester City v Southampton, Newcastle v Brentford, Brighton v Tottenham (1630)
Crystal Palace v Leeds (1300), West Ham v Fulham (1300), Arsenal v Liverpool (1530), Everton v Manchester United (1800)
Nottingham Forest v Aston Villa (1900)