Premier League champions Chelsea travel to Manchester City, last season's runners-up, on Sunday with manager Jose Mourinho embroiled in a growing row over accusations he has sidelined team doctor Eva Carneiro.
British media reports claim Carneiro will no longer attend matches or training sessions after Mourinho reacted furiously to the sight of her and physiotherapist Jon Fearn running on to the pitch to treat Eden Hazard during the latter stages of last weekend's opening 2-2 draw at home to Swansea City, which temporarily reduced Chelsea to nine players.
The outspoken Mourinho, who said that Carneiro and Fearn had been "impulsive and naive", has received widespread criticism, with Liverpool's Australian former head of sports medicine Peter Brukner branding his behaviour "absolutely appalling".
Chelsea will be without goalkeeper Thibaut Courtois, sent off against Swansea, but have a more than capable deputy in former Stoke City shot-stopper Asmir Begovic.
Both of last season's league meetings between Chelsea and their title rivals ended in 1-1 draws but City will have hope of a win after starting this campaign with an impressive 3-0 victory away to West Bromwich Albion on Monday.
Sergio Aguero may not be in their starting side after the striker played just the final 27 minutes against the Baggies following his return from international duty with Argentina.
Southampton are to set receive a double boost on Saturday when they face Everton at St Mary's.
Dutch manager Ronald Koeman is in line to return after missing last weekend's 2-2 draw with Newcastle United because of Achilles tendon surgery and the Everton game could see the Saints hand a club debut to former Chelsea midfielder Oriel Romeu.
This will be Southampton's first home league game since they signed off in May with a 6-1 victory over Aston Villa, a game marked by Sadio Mane's 176-second hat-trick, the Premier League's fastest ever.
"It was nice to end the season like that at St Mary's," Mane said. "I will try and score more than last season."
Newcastle travel to Swansea looking to build on their point against the Saints, while Tottenham Hotspur - undone by Kyle Walker's own goal in a 1-0 defeat by Manchester United - will look to bounce back at home to Stoke.
West Ham United, whose 2-0 win away to Arsenal was arguably the shock result of the first weekend, are at home to Leicester City - themselves 4-2 winners over Sunderland.
Arsenal goalkeeper Petr Cech will hope for a better second league game with the Gunners than his first, where the Chelsea great was blamed for both goals, in another London derby with Crystal Palace on Sunday.