Manchester United are aiming to derail Liverpool's bid for a quadruple and salvage a difficult second season for Erik ten Hag in Sunday's FA Cup quarterfinal.
Newcastle will need to pull off a major shock to maintain their bid for a first major trophy in 55 years when they travel to holders Manchester City.
AFP Sport highlights what to look for from this weekend's quarterfinal ties.
Wolves v Coventry (Saturday 12:15pm GMT)
A home draw against Championship side Coventry gives Wolves a huge chance to cap a fine season with a trip to Wembley.
Gary O'Neil has taken Wanderers from an expected fight for top-flight survival into challenging for Europe via both league and cup.
Wolves sit ninth in the Premier League, ahead of the likes of Newcastle and Chelsea.
However, their quest for a first FA Cup win in 64 years could be dented by injuries to a number of key players.
All of O'Neil's preferred front three of Matheus Nunes, Hwang Hee-chan and Pedro Neto are set to miss the weekend.
Coventry sit eighth in the Championship and are dreaming of Wembley once more after missing out on the Premier League in last season's playoff final.
Manchester City v Newcastle (Saturday 5:30pm GMT)
Magpies boss Eddie Howe conceded he nearly swerved off the road when he heard his side had been handed a trip to the Etihad.
Newcastle beat City at St. James' Park in the League Cup earlier this season, but Pep Guardiola's men are a different beast at home.
City are unbeaten in 38 games at the Etihad stretching back to December 2022 and have had the rare luxury of a midweek off to prepare.
Kevin De Bruyne is expected to miss out with a groin injury and City goalkeeper Ederson is sidelined with a thigh problem.
However, the English champions are strong favourites to remain on course for a second consecutive treble of Premier League, Champions League and FA Cup.
Chelsea v Leicester (Sunday 12.45pm GMT)
Chelsea's League Cup final defeat to a depleted Liverpool has piled the pressure on Mauricio Pochettino.
The Argentine has ensured a difficult first season and at times faced open revolt from the Chelsea fanbase.
However, after a slow start to the campaign at Stamford Bridge, Chelsea have lost just once in their last 13 home games.
Leicester are on course for an immediate return to the Premier League as they sit top of the Championship.
But the Foxes have hit a sticky spell at the wrong time of the season as Enzo Maresca's men have won just two of their last six games in all competitions.
Manchester United v Liverpool (Sunday 3:30pm GMT)
Ten Hag also badly needs a trophy to make a strong case not to be dismissed from the Old Trafford dugout come the end of the season.
United are languishing in sixth in the Premier League, 17 points behind their opponents this weekend.
Liverpool are involved in a thrilling three-way title race and are also into the last eight of the Europa League, having already lifted the League Cup last month.
"We won already one and we have three more left. I said it before, me personally, I want to win all four," said Reds' midfielder Dominik Szoboszlai.
However, Liverpool's brutal schedule leaves Jurgen Klopp with some tough decisions to make this weekend.
Mohamed Salah made his first club start since January 1 as a strong side finished the job over Sparta Prague in the Europa League on Thursday.
United could be boosted by the return of striker Rasmus Hojlund, who had scored seven goals in six games prior to a muscle injury.