Manchester United will seek a cure for their travel sickness when they travel to face Arsenal in an early-season blockbuster on Sunday as Liverpool take on free-scoring Aston Villa.
Newly promoted Luton play their first home match of the season against high-flying West Ham while rock-bottom Everton chase their first goal.
AFP Sport looks at some of the key talking points ahead of the weekend action.
United seek end to away-day blues
Last season's 3-2 win for Arsenal against Manchester United at a raucous Emirates was one of the most absorbing matches of the campaign.
It strengthened the Gunners' belief that they could mount a title challenge but also underlined United's struggles away from home.
Erik ten Hag's side lost all six matches away to other members of the top seven last season, conceding 3.66 goals per away match on average. The highest-placed side they beat away was 10th-placed Fulham.
A shaky opening win against Wolves at home this season was followed by a laboured, toothless performance in a 2-0 defeat away at Tottenham.
Ten Hag's task against the 2022/23 runners-up has been made more difficult by an injury crisis, with Luke Shaw, Raphael Varane and Mason Mount all unavailable.
New striker Rasmus Hojlund, who arrived at Old Trafford with an injury, could make his debut for a side once again struggling to find goals consistently.
Hot-shot Nunez stakes claim to Liverpool starting spot
Darwin Nunez had a tough first season for Liverpool after joining the club last year in a deal worth up to 100 million euros ($109 million), finding the net just nine times in the Premier League.
But the Uruguayan came off the bench last week to score two superb late goals in Liverpool's thrilling 2-1 win against Newcastle in a performance that could mark a turning point in his Anfield career.
Manager Jurgen Klopp admitted the former Benfica striker was "obviously fired up" after being named as a substitute once again.
Now the German has a choice to make against Unai Emery's Villa after favouring Luis Diaz, Mohamed Salah, Diogo Jota and Cody Gakpo in the first three matches of the season.
"It's clear he's not happy," said Klopp. "It's early in the season, we need to find stability and results.
"He will play, there's no doubt about that. We need everyone. We need to find a way of playing. This is a new team with new key players. It needs time."
Luton seek home comforts
Luton have had a tough start on their return to the English top flight after three decades away, shipping four goals against Brighton and three against Chelsea.
The club's opening Premier League home game against Burnley was postponed due to work taking place to upgrade their quirky Kenilworth Road ground.
But on Friday they will host the Hammers after climbing all the way up from the fifth-tier National League over the past decade.
Work on the ground – where the entrance to the away end is built into a row of traditional red-brick terraced houses – will lift numbers just above Bournemouth's 11 307-capacity Vitality Stadium, meaning Luton will not have the smallest ground in the division.
The Hatters are one of four teams still stuck on zero points and will be desperate to get off the mark.
But they have a tough task against David Moyes' West Ham, who are second in the table after wins against Chelsea and Brighton.
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