Man City face Liverpool summit meeting as Everton fight for survival
Arsenal have a chance to top the table depending on results elsewhere, while Tottenham host high-flying Aston Villa.
AFP Sport picks out three talking points ahead of the action as the English top flight returns following the international break.
Liverpool seek to end Man City run
Liverpool have been the only team to consistently challenge Manchester City in recent years, winning 10 out of 23 matches in all competitions under the reign of Jurgen Klopp.
The two sides had epic battles in the 2018/19 and 2021/22 seasons, when City pipped their rivals by just a single point on both occasions, while the Reds clinched their first league title in 30 years in 2020.
But Liverpool, revitalised after a below-par campaign last season, have not won a league game at the Etihad since their 4-1 demolition of City in November 2015.
The reigning champions, by contrast, have won 23 matches in a row at home in all competitions.
Erling Haaland is one goal away from obliterating the Premier League record for the quickest player to 50 goals - the Norwegian scored twice in City's frantic 4-4 draw at Chelsea earlier this month to take his tally to 49 goals in just 47 appearances.
Former Newcastle and Manchester United forward Andrew Cole is the current record holder, reaching the landmark in 65 games.
Will 10-point penalty fire up Everton?
Sean Dyche's Everton had turned the corner in recent weeks, winning three of their past five games to pull well clear of the relegation zone.
But last week's 10-point deduction for breaching Premier League profitability and sustainability rules means they go into their match against Manchester United level on four points with bottom club Burnley.
Everton director of football Kevin Thelwell said the team would now have added motivation, fuelled by a burning sense of injustice at the "wholly disproportionate ruling".
Despite the sanction, the nine-time English champions are just two points from safety, thanks to the poor form of the newly promoted teams.
United have climbed to sixth in the table after winning four of their past five league games but they are blunt in attack and remain unconvincing at the back.
Spurs seek to stop rot against in-form Villa
Tottenham boss Ange Postecoglou made the best start to a season by a new manager in Premier League history after 10 games but the team has dropped off top spot due to consecutive defeats.
Spurs were beaten 4-1 by Chelsea after being reduced to nine men and then lost 2-1 at Wolves in a game in which they were leading going into stoppage time.
One headache Postecoglou must deal with is the absence of playmaker James Maddison, who has made such an impact since arriving in June but has been ruled out until the New Year with an ankle injury.
Postecoglou will be wary of Aston Villa, who have continued their rapid progress under Unai Emery and are just a point behind fourth-placed Spurs and three points off the top.
The Birmingham club's 3-1 win against Fulham earlier this month was a 13th successive home win - a feat they last achieved 40 years ago.
But their away form is less impressive, with just two wins from six games on the road.
Fixtures
Saturday (3pm GMT unless stated)
Manchester City v Liverpool (12.30pm), Burnley v West Ham, Luton v Crystal Palace, Newcastle v Chelsea, Nottingham Forest v Brighton, Sheffield United v Bournemouth, Brentford v Arsenal (5.30pm)
Sunday
Tottenham v Aston Villa (2pm), Everton v Manchester United (4.30pm)
Monday
Fulham v Wolves (8pm)