Manchester United face old nemesis Vincent Kompany at Burnley this weekend in desperate need of a Premier League win while Arsenal host in-form Tottenham in a tantalising north London derby.
Struggling Chelsea take on Unai Emery's Aston Villa and new-look Liverpool will look to make it five wins in a row against West Ham.
AFP Sport picks out three talking points ahead of the action in the English top flight.
Man Utd's away-day blues
A trip to newly promoted Burnley would not usually strike fear into Manchester United hearts -- they have only lost twice against the Clarets since 1968.
But Erik ten Hag's team are leaking goals, struggling to score and desperately low on confidence.
The 13th-placed Red Devils have now lost 18 of their past 35 away matches in all competitions and pre-season belief has evaporated, with the club beset by problems on and off the pitch.
Lying in wait on Saturday are Kompany's Burnley, who are yet to win in the top flight since their promotion.
The former Manchester City captain will be desperate to pile on the pain for the Old Trafford club.
A frustrated Ten Hag, speaking after this week's 4-3 defeat at Bayern Munich, said his team "have to look in the mirror" after costly defensive errors.
"You have to suffer sacrifices in such situations and to give everything and to stop it," said the Dutchman. "And only when we get that in, will we win games."
Revitalised Spurs eye Arsenal scalp
Tottenham are thriving under new boss Ange Postecoglou -- sitting second in the Premier League table, two places above bitter rivals Arsenal on goal difference.
Spurs laboured to an eighth-place finish last season after an underwhelming campaign during which they parted ways with Antonio Conte, but Postecoglou has transformed the mood.
Tottenham captain Son Heung-min is eager to right the wrongs after Arsenal completed a first league double in the fixture last season since 2014 and he feels the Gunners will be wary of his team.
"It's going to be a really difficult game but they won't want to face us at this time," said the South Korean forward.
"We just have to give it everything we have and it will be a difficult game for both sides, but we're looking forward to this game because it's the right time to play against them. We'll have a good game."
Arsenal have not yet recaptured the fluency that fired their ultimately unsuccessful title tilt last season.
But they are just two points behind leaders and defending champions Manchester City and will make the short journey to the Tottenham Hotspur Stadium lifted by a sparkling 4-0 win over PSV Eindhoven in midweek.
Toothless Chelsea
The spotlight on the crisis at Manchester United has helped take the heat off Chelsea boss Mauricio Pochettino but the Blues are languishing in 14th spot in the Premier League table.
The Stamford Bridge side are once again struggling to find the net -- they have failed to score in their past two matches and have won just twice in the league since March.
For all their eye-wateringly expensive recruitment, six of their substitutes for last week's 0-0 draw with Bournemouth had no Premier League experience.
"We know what we need to do, we are strong in our belief," Pochettino said after the stalemate. "We have 12 injured and today we had three or four young guys and two keepers on the bench."
But the former Tottenham and Paris Saint-Germain boss will be painfully aware that Chelsea are not a patient club as he prepares his team to face seventh-placed Villa.
They sacked Thomas Tuchel in the early weeks of last season and Graham Potter suffered the same fate in April, when the club were 11th in the table.
Fixtures
Saturday (1400 GMT unless stated)
Crystal Palace v Fulham, Luton v Wolves, Manchester City v Nottingham Forest, Brentford v Everton (1630), Burnley v Manchester United (1900)
Sunday (1300 unless stated)
Arsenal v Tottenham, Brighton v Bournemouth, Chelsea v Aston Villa, Liverpool v West Ham, Sheffield United v Newcastle (1530)
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