Tottenham host Arsenal at Wembley this weekend aiming to crush the optimism created by the Gunners' new-look forward line while the absent Riyad Mahrez will be missed by both teams at the Etihad.
Elsewhere, Antonio Conte's Chelsea welcome West Brom with the Italian manager's job looking precarious following embarrassing back-to-back defeats to Bournemouth and Watford.
Leaders Manchester City host Leicester, who will again be without Mahrez after he failed to force through a move to the Premier League leaders, while Manchester United travel to Newcastle and Southampton welcome back Virgil van Dijk in a Liverpool shirt.
AFP Sport picks out three major Premier League talking points this weekend.
Spurs to smother high-octane Arsenal?
Excitement coursed around the Emirates last weekend as Arsenal's club-record signing Pierre-Emerick Aubameyang scored on his debut and Henrikh Mkhitaryan conjured three assists in a 5-1 demolition of Everton.
A tougher task awaits at Wembley on Saturday against a high-flying Tottenham side, who have not lost in 11 games.
Spurs are currently in fifth but would climb into third - at least temporarily - with victory and move seven points ahead of sixth-placed Arsenal.
Mauricio Pochettino's squad looks in fine shape to handle the demands of three competitions in the coming months with the return of Erik Lamela, Victor Wanyama, Harry Winks and Serge Aurier from injury to complement the arrival of Lucas Moura from Paris Saint-Germain.
"Now we are 24 players and it will be tough to find a place in the starting XI for everyone - 24 players that fight to be on the starting XI every single game," said the upbeat Spurs boss.
Mahrez missed by both City sides
Riyad Mahrez could have been lining up for Manchester City this weekend and he should certainly be playing for Leicester.
Saturday's match at the Etihad will be the third consecutive league game the winger has missed since Pep Guardiola's City failed to get their man on January 31, transfer deadline day.
Mahrez, 26, has not even trained with the mid-table Foxes since his dream move to the Premier League leaders collapsed.
"Riyad is not available for Saturday's game," said Leicester boss Claude Puel, adding that he hoped the player could "get his head right" and return to the fold.
Guardiola's men could also do with extra numbers in attack as they prepare for a run of four games in four different competitions before the end of the month.
Guardiola named just six substitutes for last weekend's draw at Burnley, protesting that he did not have the numbers due to an injury crisis, particularly in attacking areas, with the club forced to deal with lengthy layoffs for Leroy Sane and Gabriel Jesus.
Conte's last stand?
Antonio Conte said he would not lose sleep over the possibility of losing his job following a 4-1 defeat at Watford and he has a great chance to turn the corner with a match against bottom club West Brom at Stamford Bridge on Monday.
With a series of ominous-looking ties looming, failure to win could see a new boss put in charge for the business end of the season at a club used to dispensing with their managers just months after winning silverware.
Chelsea face Barcelona in the first leg of their Champions League last-16 tie on February 20 before visiting both Manchester United and Manchester City in the league and then making the return trip to the Camp Nou on March 14.
Rafael Benitez, Avram Grant, Roberto di Matteo and Guus Hiddink (twice) have been drafted in to tide Chelsea over during the Roman Abramovich era.
Di Matteo won the club's only Champions League title in 2012, Benitez bagged the Europa League in 2013, Hiddink claimed the 2009 FA Cup and Grant was a penalty shootout away from winning the Champions League in 2008.
Fixtures (1500 GMT unless stated)
Tottenham Hotspur v Arsenal (1230 GMT), Everton v Crystal Palace, Stoke v Brighton, Swansea v Burnley, West Ham v Watford, Manchester City v Leicester City (1730 GMT)
Huddersfield Town v Bournemouth (1200 GMT), Newcastle United v Manchester United (1415 GMT), Southampton v Liverpool (1630 GMT)
Chelsea v West Brom (2000 GMT)
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