Liverpool's new-look midfield faces a stern examination as the Reds put their Premier League title aspirations to the test at Newcastle on Sunday, while Manchester United aim to kickstart their campaign against Nottingham Forest.
Title rivals Manchester City and Arsenal are two of only three sides with six points from their opening two games of the new campaign.
But it is Brighton who top the table after shrugging off the sales of key midfielders Alexis Mac Allister and Moises Caicedo to score eight goals in their opening two games.
Liverpool's failure to beat Chelsea to Caicedo or Romeo Lavia has seen their transfer business heavily criticised by many of their own fans.
The Reds instead landed 30-year-old Japan captain Wataru Endo as their replacement for the departed Fabinho and Jordan Henderson.
Endo, described by Liverpool boss Jurgen Klopp as a "real monster", could make his first start at St James' Park in an early indicator of who could rival City and Arsenal for the title.
Newcastle leapfrogged Liverpool into the top four last season despite the Reds winning both clashes between the sides.
The Magpies thrashed highly-fancied Aston Villa 5-1 at home on the opening weekend of the campaign, but were brought back down to earth by an inability to match champions City in a 1-0 defeat at the Etihad Stadium.
Liverpool will have Mac Allister available after his red card on his home debut in a 3-1 win over Bournemouth was rescinded.
Mount's absence a solution for Man Utd?
Hope that United can challenge for their first league title in 11 years has already dwindled after a sloppy 2-0 defeat at Tottenham followed a woeful performance at home to Wolves, despite escaping with a 1-0 win on that occasion.
Erik ten Hag's men have suffered from a lack of cutting edge up front in the absence of new striker Rasmus Hojlund, out with a back injury.
The Dane misses the visit of Nottingham Forest on Saturday, but another injury to Mason Mount may simplify things for Ten Hag.
Fitting captain Bruno Fernandes and Mount, a close-season signing from Chelsea, into the same midfield has proved problematic in the opening weeks of the season.
United lost just two of 25 games in which the trio of Fernandes, Cristian Eriksen and Casemiro started in midfield last season.
Two of the three clubs to lose their opening two games face off on Saturday when troubled Everton host Wolves at Goodison Park.
Everton have narrowly avoided the drop for the past two years and look set for another season of suffering, with Sean Dyche trying to patch the holes in his squad on a shoestring budget by Premier League standards.
The Toffees' troubles on the field have been compounded by the collapse of a deal this week for an American investment group to inject capital into the club for a 25 percent stake.
"It's just the way Everton's been for a number of months, years even," said Dyche. "It's our job to change the story. It always starts on the pitch, with me and the team changing the rhetoric."
Wolves' own financial problems led to the departure of manager Julen Lopetegui who resigned on the eve of the season.
A dominant performance in Gary O'Neil's first game in charge went unrewarded at Old Trafford, but optimism from that display was wiped away in a 4-1 thrashing at home to Brighton last weekend.