Gabriel Jesus (right) returned to action for Arsenal in the 3-0 win against Fulham. AFP
Tottenham will leapfrog third-placed Manchester United if they beat struggling Southampton while Newcastle can strengthen their push for a Champions League place by seeing off Nottingham Forest.
At the other end of the table, just five points separate 12th-placed Crystal Palace from basement club Southampton.
AFP Sport looks at some of the key talking points ahead of the weekend's action in the English top flight.
Arsenal eye clear blue water
A month ago Manchester City beat Arsenal 3-1 to go top of the Premier League table as Mikel Arteta's men wobbled.
Now the Gunners can pull eight points clear of the defending champions if they beat Palace at the Emirates on Sunday.
Arsenal have won all five league games since their defeat to City -- their only loss at home this season -- while their closest rivals dropped two precious points against Forest.
A 3-0 victory at Fulham last weekend was the 100th win of the Arteta era, which started in 2019.
It came in the Spaniard's 168th game in charge, meaning his overall win percentage of 59.5 is the highest for any Arsenal manager in history.
Arteta has been deprived of the services of Eddie Nketiah, who is out of action with an ankle injury, but Gabriel Jesus returned to action last week following knee surgery to add more firepower.
January signing Leandro Trossard has also made a big impact in the final third -- the Belgian provided all three assists at Fulham.
Champions League battle
Behind Arsenal and City, the race is also on for the two remaining places in next season's Champions League.
Manchester United, in FA Cup quarter-final action this weekend, appeared to have a strong grip on third but that has been loosened after their 7-0 pummelling by Liverpool and a disappointing goalless draw against Southampton.
Victory at Southampton on Saturday would lift Antonio Conte's Spurs one point above United, though they would have played two games more.
Draw specialists Newcastle beat Wolves 2-1 last week to reignite their top-four push after a spell in which they won just one of eight league games.
"We'd gone a few weeks without that feeling -- we wanted to return to our best and I felt we did," said Newcastle boss Eddie Howe. "Hopefully we can build on it."
Liverpool and Brighton are not in action this weekend, meaning Brentford would go sixth if they condemn Leicester to a fifth straight defeat in all competitions.
The relegation battle is too close to call and no team below Aston Villa in 11th spot will feel safe.
West Ham and Leicester have been used to challenging for European football in recent seasons but both sit outside the bottom three only on goal difference.
Leicester boss Brendan Rodgers remains defiant that his side can find their mojo again after showing "resilience" to recover following a poor run earlier in the season.
With West Ham not playing, all of the bottom three could end the weekend outside the relegation zone.
Bournemouth are aiming to build on a 1-0 win over Liverpool last weekend when they travel to Villa, while Leeds, with just one victory in their past 13 league games, are away to fellow strugglers Wolves.
Everton are a point clear of the drop zone thanks an uptick in form under Sean Dyche, but face a tough trip away to a revitalised Chelsea.
Palace have not won this year and have failed to even score in their past four games.
"Our front players have to change their mindset. We have to be more aggressive going forward," said Palace boss Patrick Vieira ahead of his return to Arsenal, whom he captained the last time the Gunners won the Premier League in 2003/04.
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