Manchester City host Arsenal in a showdown between the Premier League title favourites on Sunday, while Tottenham boss Ange Postecoglou badly needs a win when his side host Brentford.
Liverpool are looking to bounce back from a shock home defeat to Nottingham Forest when Bournemouth visit Anfield and Manchester United seek revenge with a trip to Crystal Palace.
AFP Sport looks at the pick of this weekend's Premier League action.
A battle between the top two pits the unstoppable force in City's in-form striker Erling Haaland against the immovable object in Arsenal's obturate defence.
Haaland has struck a Premier League record nine times in the opening four games of the season.
But Arsenal have only conceded once, when down to 10 men against Brighton, and kept clean sheets already away at Aston Villa and Tottenham.
The top two in each of the past two seasons already occupy those positions once more.
"It's another unbelievable team that defend really well," said City boss Pep Guardiola. "They don't concede chances, they don't concede goals. In many aspects they control everything.
"Was the biggest challenge for the title the last two seasons, they are there and will be there for many years because they created a depth of squad and a young team."
City are the only side with a perfect 12 points so far, but a depleted Arsenal made sure they are only two points behind by grinding out a 1-0 victory over Spurs in last weekend's north London derby.
The Gunners are set to be missing captain Martin Odegaard once more due to an ankle injury but can welcome back Declan Rice from suspension.
City are also set to be without their creative hub as Kevin De Bruyne limped out of Wednesday's 0-0 Champions League draw against Inter Milan.
Arsenal's third consecutive away derby win at Tottenham ramped up the scrutiny on Postecoglou.
Spurs have taken only four points from their opening four Premier League games of the season and their form has been trending downwards for some time.
After a blistering start under the former Australia manager, Tottenham have won just 13 of their last 32 league games, including seven defeats in the last 11.
Postecoglou has insisted he will deliver silverware in his second season in charge but narrowly avoided a League Cup exit to second-tier Coventry in midweek.
With trips to Manchester United and Brighton to come, Spurs need to steady the ship against a Brentford side that troubled City last weekend in a 2-1 defeat.
What a difference a week has made for United boss Erik ten Hag.
The Dutchman returned from the international break under pressure after back-to-back defeats to Brighton and Liverpool.
But two victories and 10 goals against Southampton and Barnsley has lifted the mood ahead of the trip to Palace.
The low point of a dismal league campaign last season arguably came in a 4-0 thrashing by the Eagles in May.
But Ten Hag believes this weekend will be a different story as he is now blessed with options rather than fighting an injury crisis.
"It was a 4-0, totally deserved, but Saturday will be different," said Ten Hag. "From February onwards, we had to find 11 players to construct a team.
"Now it is 18 and we can pick one."
Fixtures (all times GMT)
Saturday
West Ham v Chelsea (1130), Aston Villa v Wolves, Fulham v Newcastle, Leicester v Everton, Liverpool v Bournemouth, Southampton v Ipswich, Tottenham v Brentford (all 1400), Crystal Palace v Man Utd (1630)
Sunday
Brighton v Nottingham Forest (1300), Man City v Arsenal (1530)
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