Under-fire Manchester United boss Erik ten Hag cannot afford another damaging defeat when his troubled side face Fulham on Saturday.
Tottenham's Premier League title challenge will get an intriguing test as the leaders' former boss Mauricio Pochettino returns with Chelsea.
Arsenal also harbour title aspirations, making their showdown with top-four contenders Newcastle one of the weekend's marquee match-ups.
Crisis-torn Man Utd have to 'stand up’
Erik ten Hag urged his Manchester United flops to "stand up" to the pressure as the Dutch coach battles to stop their season imploding.
United have made their worst start since 1962-63 and a loss against Fulham at Craven Cottage could push Ten Hag to the brink of the sack after less than two seasons in charge.
Hammered 3-0 by Manchester City last weekend, United were brushed aside by the same score against Newcastle in the League Cup fourth round on Wednesday.
Ten Hag's men have lost eight of their 15 matches in all competitions this term, leaving them eighth in the Premier League and in danger of failing to reach the Champions League last 16.
It is the first time United have lost successive home games by three goals or more since 1962, while they have lost five of their first 10 home games for the first time since 1930-31.
"This is not good enough and we know that. That's below our standards and we know that all and we have to take responsibility for this," Ten Hag said after United were booed off against Newcastle.
Bookmakers' odds on Ten Hag being axed have been slashed amid reports of players losing patience with their manager's hardline personality.
In a desperate plea for unity, the former Ajax boss said: "That is our job. We sleep and we have to go again, so we have to stand up.
"Sticking together is the only way, the only way we do it, shoulder by shoulder, then we will come through this."
'Confident' Postecoglou revives Spurs
James Maddison says Ange Postecoglou's confident sales pitch convinced him to join Tottenham, laying the foundations for the club's surprise title bid.
Postecoglou's upbeat assessment of Tottenham's future persuaded Maddison to ignore other suitors when he left Leicester in the close season.
It has proved an inspired move for both Maddison and his manager as the England playmaker's exemplary form has fuelled unbeaten Tottenham's climb to the top of the table.
"He said 'James, whether you decide to come or not, you're going to see a completely different Tottenham team'," Maddison said ahead of Monday's clash with Chelsea manager Mauricio Pochettino, making his first return to the club who sacked him in 2019.
"I just loved the confidence he said that with. And that just left that bit in my mind where I thought, yeah, I want to go and work for this guy.”
Arsenal ready for Newcastle test
As they chase their first Premier League title since 2004, a win at Newcastle would rank as a significant statement of intent for second-placed Arsenal.
Gunners boss Mikel Arteta took the blame after his decision to make six changes backfired in Wednesday's League Cup defeat at West Ham.
But that setback will quickly be forgotten if Arsenal, who sit two points behind Tottenham, return from Tyneside with a valuable victory over a team on a high after their League Cup triumph at Manchester United.
"It's great that the game is in three days because it's a chance to turn things around. We can go and try to put things right," Arsenal midfielder Jorginho said.
"The only thing we can take from this tough result is how we need to be much better at competing for the next game, because if you're going to play at this level, you won't win for sure."
Fixtures (1500 GMT unless stated):
Saturday
Fulham v Manchester United (1230), Brentford v West Ham, Burnley v Crystal Palace, Everton v Brighton, Manchester City v Bournemouth, Sheffield United v Wolves, Newcastle v Arsenal (1730)
Sunday
Nottingham Forest v Aston Villa (1400), Luton v Liverpool (1630)
Monday
Tottenham v Chelsea (2000)
AFP