On a day of derbies in north London and Merseyside, the fate of Manchester United will be the most anticipated result on Saturday. United host West Ham having won just one of their opening five Premier League games, including a 5-3 collapse at Leicester last weekend.
"It's happened, it's about overcoming things," said manager Louis van Gaal, who has yet to halt the decline from the season under David Moyes.
For all the attacking firepower at Louis van Gaal's disposal - from Angel di Maria to Radamel Falcao - Van Gaal is down to just one fit center back, Marcos Rojo, to face West Ham at Old Trafford.
Jonny Evans was out with an ankle injury, Tyler Blackett was suspended following his dismissal at Leicester, Chris Smalling was injured in training, and Phil Jones was sidelined with a hamstring problem. Either Daley Blind or fellow midfielder Darren Fletcher might have to be shifted back into defence.
"All the three right-sided center halves are out - I don't know how long they will be out for," Van Gaal said on Thursday. "Evans is a very difficult one. His bone is bruised a lot and we have to wait and see, to evaluate it.
"Smalling yesterday ran out of the training session because he had stiff legs. We have to see what that means. But I don't take risks with players."
Another six players are also injured, including midfielders Michael Carrick and Marouane Fellaini, and winger Ashley Young.
"I have never been in this situation before (with injuries)," Van Gaal said. "It is strange. For me it's difficult to understand. We are evaluating what we can do in a different way."
United-West Ham is one of 10 games this weekend. Here are some things to know about the other games:
NORTH LONDON DERBY
For all the talk that the balance of power might shift in London, Arsenal remain the dominant force, with Tottenham in their wake. They meet at the Emirates Stadium separated by two points, but few would bet against Arsenal remaining in the top four come May.
Tottenham have won just twice at Arsenal since the inaugural Premier League season in 1992-93. Mauricio Pochettino's side goes into the game having taken just one point from last three league games.
"We have a lot of work to do to improve the concept of the team," the former Southampton manager said ahead of his first north London derby. "But we are going in the right way and we need to show our work from the training ground and in the training sessions and produce that in the game."
LACKLUSTER LIVERPOOL
The first game of the round six sees Liverpool host Everton, struggling without Luis Suarez, who joined Barcelona in the offseason, and injured striker Daniel Sturridge. Liverpool have collected just six pointed from a possible 15 so far, losing back-to-back league games against Aston Villa and West Ham going into Saturday's derby.
But Everton hasn't won at Anfield for 15 years and lost last weekend to Crystal Palace.
CHELSEA'S CHASE
Early pacesetter Chelsea find themself in the unusual position of hosting an Aston Villa side alongside the London club in the top four on Saturday.
"They've had a great start to the season, apart from their last result (losing at Arsenal), so it's going to be another tough test for us," said Chelsea defender Gary Cahill, who has played for Villa.
Chelsea remain unbeaten after drawing at Manchester City last weekend.
"If you have a couple of sticky results it puts the pressure on going into games," Cahill said. "But at the moment we're unbeaten, we're going well and we should have confidence."
ELSEWHERE...
Champion Manchester City travel to Hull, Crystal Palace host Leicester and Southampton take on Queens Park Rangers.
Sunderland, Burnley and Newcastle are still searching for their first wins. Sunderland host Swansea on Saturday, Burnley travel to West Bromwich Albion on Sunday, and Newcastle are at Stoke the following night.
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