Steven Gerrard's debut after leaving the Glasgow Rangers for Aston Villa will probably attract most of the attention as he looks to end the run of five defeats that cost Dean Smith his job.
Villa entertain Brighton and much of the attention will be to see if Gerrard can bring the best out of players such as Leon Bailey and Emi Buendia, but he also needs others such as John McGinn and Tyrone Mings to be at their best against a rival that is likely to have most of the ball.
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Dean Smith was out of work for eight days before he was confirmed as the replacement for Daniel Farke at bottom of the table Norwich City and Smith makes his Norwich debut at home to Southampton, reports Xinhua.
The irony of the fixture calendar means that Smith's first game as Norwich City coach is against the same team that defeated Aston Villa in his last game in charge there and who have won their last two games 1-0.
Eddie Howe is the final debutant of the weekend, as Newcastle United continues to look for their first win of the season at home to a Brentford side that is suddenly in trouble after four consecutive defeats.
Brentford travel north with several players out injured and it looks like the ideal moment for Howe to get off to a flying start in front of an expectant St James' Park.
League leaders Chelsea are first into action this weekend with a visit to play Leicester City, who will be without the influential Youri Tielemans.
Manchester United coach Ole Gunnar Solskjaer needs a relatively calm afternoon when his side visits Watford. Home defeats to Liverpool and Manchester City have left Solskjaer's men chastened, but they should have too much firepower for a rival that has lost three out of four games since Claudio Ranieri replaced Xisco Munoz at the helm.
Liverpool against Arsenal also promises to be a fascinating match as Mikel Arteta's side measures a recovery that has seen them win four and draw two of their last six matches at Anfield.
Much of Arsenal's recent good form is down to their defensive solidity with Gabriel and Ben White in defense, but they will have to be at their best to keep Mohamed Salah and company at bay.
West Ham flew striker Michail Antonio back in a private jet from Jamaica to ensure he would be fully fit for Saturday's visit to play Wolves and David Moyes' side can be expected to cause Wolves a lot of problems from set-pieces as they did against Liverpool a fortnight ago.
Burnley seem to slowly be recovering from their dreadful start to the season with just one defeat in six games and Sean Dyche's men will be hoping to climb out of the bottom three with a win over Crystal Palace, who will face a physical battle at Turf Moor.
Sunday has two games with Manchester City entertaining Everton, who are without a win in their last five league matches, before the weekend's last match will put Harry Kane in the spotlight for Antonio Conte's home debut as Tottenham coach.
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Kane netted seven goals in 108 minutes for England during the international break, but so far, he has only one league goal this season. The visit of Leeds United looks like the moment for Kane to carry that form over for his club and put a difficult early-season behind him.