Liverpool and Arsenal will move on from their midweek European tussles and put lengthy unbeaten Premier League runs on the line when they host their bitter rivals this weekend.
The Reds take on Everton in the Merseyside derby while Arsenal host north London neighbours Tottenham Hotspur.
Also, Huddersfield's Aaron Mooy – fresh from his brace against Wolverhampton last weekend – will look to add to his season tally when Socceroos teammate Mat Ryan's Brighton & Hove Albion visit Kirklees Stadium, while Manchester United are away to struggling Southampton.
Manchester City look to continue their undefeated start when they host Bournemouth as Chelsea hope to bounce back from their first loss of the season to Spurs against bottom side Fulham, who won under new manager Claudio Ranieri last week.
Liverpool are undefeated in the league and sit two points behind league leading champions City.
The Reds are coming off a 2-1 loss at Paris Saint-Germain on Wednesday that left their Champions League status hanging in the balance, but there's no need to use that as motivation, according to manager Jurgen Klopp.
"Come on, it's a derby, we don't have to show a reaction," he said after the PSG game. "This game is isolated from the season: it's a derby, it's at home."
Everton are winless in 17 games against Liverpool and haven't won at Anfield since September 1999.
But the Toffees are in good form, having lost just one of seven in the league to climb up to sixth.
"I think all the boys have been looking forward to the derby since the start of the season and that feeling has grown with the performances we have been putting together over the past couple of months," Gylfi Sigurdsson told evertontv.
Arsenal are unbeaten on two fronts: 11 games in the league and 18 overall following their Europa League victory at Vorskla.
But they've won just one of their past eight league meetings with Tottenham, that coming last season at home.
Spurs will be looking to continue an impressive run in which they handed Chelsea their first league defeat and beat Inter Milan to keep their Champions League hopes alive.
"We know it is more than a game for both clubs and for both [sets of] fans," goalkeeper Hugo Lloris told Sky Sports.
"Now we have time to recover and to prepare as well as possible but that type of game you play more with passion and desire."
Cardiff host Wolves, Burnley visit Crystal Palace, Watford are at Leicester and Newcastle take on West Ham in the other games.
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