Premier League leaders Arsenal went into the international break with an eight-point advantage, and the Gunners will be hoping for a favour from Liverpool on Saturday.
Before Arsenal host strugglers Leeds United, Liverpool travel to the Etihad Stadium to face second-placed Manchester City.
Pep Guardiola's side have a game in hand on Arsenal, but surely they must beat the Reds to give themselves a realistic chance of retaining the title.
Elsewhere, there are more huge fixtures at the bottom of the table, including West Ham v Southampton, while Newcastle United and Manchester United play in a repeat of February's EFL Cup final.
Manchester City v Liverpool
Liverpool, who won the reverse league fixture 1-0, are looking to complete the league double over City for what would be just a second time in the last 17 seasons, previously doing so in Jurgen Klopp's debut campaign in 2015-16.
Mohamed Salah has scored in all three of Liverpool's games against Man City this season, in the Premier League, Community Shield and EFL Cup. The last Liverpool player to score in four different games against an opponent in a single campaign was Ian Rush, netting in five meetings with Everton in 1986-87.
Erling Haaland has scored 42 goals in all competitions for City this season, including six hat-tricks (all at the Etihad). Only two players have scored more in a single campaign for a Premier League club (since 1992-93) – Ruud van Nistelrooy in 2002-03 and Salah in 2017-18 (both 44).
Best bet – City to avoid defeat: City have lost just one of their last 13 Premier League home games against Liverpool (W7 D5), going down 4-1 in November 2015 under Manuel Pellegrini. Guardiola's team have won their last three top-flight games, but have yet to win four in a row this season.
Long shot – Liverpool to win: Liverpool have won more Premier League games against reigning champions than any other side (23). They are aiming to achieve their first such double since 2013-14, beating Manchester United 1-0 at home and 3-0 away. However, they have taken just 12 points from their 13 Premier League away games this season (W3 D3 L7), compared to 30 at home.
Opta prediction: Despite the fierce rivalry over recent years, City are the big favourites for this game, with Opta's supercomputer ranking their chances of victory at 50.9 per cent. The draw is at 26.4 per cent, with Liverpool handed a 22.7 per cent chance of success.
Arsenal v Leeds United
Leeds have won just two of their 23 Premier League games against the league leaders (D9 L12), though both victories came away from home (v Middlesbrough in August 2000 and Man City in April 2021). They have lost all four such games against Arsenal by an aggregate score of 14-2.
Arsenal have won their last six Premier League games, their joint-longest such run under Mikel Arteta. They last won seven in a row between August and October 2018 under Unai Emery.
Arsenal’s top scorer in the Premier League this season is Gabriel Martinelli with 13 goals. The last player to score more while aged 21 or under in a single campaign in the division was Dele Alli in 2016-17 (18).
Best bet – Bukayo Saka to score or assist: Only Erling Haaland (33) and Harry Kane (23) have been involved in more Premier League goals than Saka this season (22), with the winger the only player so far to reach double figures for both goals (12) and assists (10).
Long shot – Leeds to keep a clean sheet: Since a 0-0 draw in their first Premier League away game against Arsenal in February 1993, Leeds have not drawn or kept a clean sheet in any of their subsequent 13 league visits to the Gunners (W3 L10), shipping 31 goals in total.
Opta prediction: Opta do not give Leeds much chance at Emirates Stadium (15.5 per cent). Arsenal are huge favourites, with a 61.6 per cent win probability, while the draw is ranked at 22.9 per cent.
West Ham v Southampton
Coming into this weekend's games, Southampton have picked up the highest share of their Premier League points this season away from home (57 per cent - 13/23). Meanwhile, only Nottingham Forest (77 per cent) have a higher share of points won at home in 2022-23 than West Ham (75 per cent - 18/24).
Southampton have picked up as many points in their six Premier League games under Ruben Selles (8 – W2 D2 L2) as they had in their 17 league matches beforehand (W2 D2 L13).
Sides starting the day bottom of the Premier League have won 11 league matches this season, four more than the whole of last term (seven), and the most in a single campaign in the competition since 2017-18 (12). Southampton have been responsible for three of those victories by bottom-placed sides in 2022-23, a joint-high (also Leicester).
Best bet – James Ward-Prowse to create two chances: Coming into this weekend's games, only Kieran Trippier (49) has created more chances from set plays than Ward-Prowse (35) in the Premier League this season, while the Southampton captain is the only player to create 25+ chances from both open play (27) and set pieces (35) in the division this term.
Long shot – A goalless draw: No other sides have kept fewer clean sheets in the Premier League this season than Southampton (four) and West Ham (five)
Opta prediction: Despite both of these teams struggling, it is West Ham who Opta give 51.4 per cent chance of claiming all the points. Southampton have been responsible for three of the seven victories by the bottom-placed side this season, but the likelihood of them succeeding this time stands at 21.7 per cent.
Newcastle United v Manchester United
Following their goalless draw at Old Trafford in the reverse fixture, Newcastle are looking to keep a clean sheet in consecutive Premier League games against United for the first time since May 1997.
No player has scored more winning goals in the Premier League this season than Marcus Rashford, with nine of his 14 strikes being the winner. Only two United players have ever scored more winning goals in a single campaign in the competition – Cristiano Ronaldo (12 in 2007-08) and Wayne Rooney (10 in 2009-10).
Coming into this weekend's fixtures, only Bournemouth (38), Nottingham Forest (32) and Leicester (30) have conceded more away goals in the Premier League this season than United (27). Indeed, only in four different Premier League campaigns have the Red Devils conceded more on the road – 1999-00 (29), 2001-02 (28), 2018-19 (29) and 2021-22 (35).
Best bet – United to win: United have won more Premier League away games against Newcastle than any other side (14). However, they have lost two of their last five such visits (W2 D1), having lost just one of their previous 13 at St James' Park. Newcastle are winless in six Premier League games against Man Utd (D2 L4), though the last two have both been drawn.
Long shot – Rashford and Alexander Isak to score: Rashford has been involved in seven goals in his eight Premier League starts against Newcastle (four goals, three assists) – only against Arsenal and Leicester City (nine each) has he been involved in more. Isak, meanwhile, has scored six goals in 10 Premier League appearances for Newcastle this season, including three in his last two.
Opta prediction: This could prove a big game in the top-four race, with Newcastle only three points behind third-placed United. The visitors are made very slight favourites (36.8 per cent to 34.2 per cent). The draw is given a 29 per cent chance.