After starting Premier League wins over Newcastle United and Sheffield United, Grealish was a surprise omission from Saturday's matchday squad.
The 27-year-old was ruled out with a slight thigh problem, adding to Man City's current injury list which includes Kevin De Bruyne and John Stones.
In Grealish's absence, Jeremy Doku was presented with his Man City debut after completing a £55m move from Rennes last month.
Man City went on to claim a 5-1 victory over the Cottagers thanks to efforts from Julian Alvarez and Nathan Ake, before Erling Haaland netted a second-half hat-trick.
With Pep Guardiola recovering from minor back surgery, Man City's stand-in boss Juanma Lillo was able to provide an update on Grealish's status after the game, suggesting he is unlikely to join up with the England squad.
Speaking to reporters, Lillo said: "It's going to be difficult for Jack to make it, but I'm not a doctor and it will be difficult for me to explain."
Grealish was named in Gareth Southgate's squad earlier this week alongside Man City teammates Kyle Walker, Kalvin Phillips and Phil Foden.
The Three Lions are set to face Ukraine in Euro 2024 qualifying on September 9, before they travel to Hampden Park for a friendly with Scotland three days later.
Grealish, who has earned 32 caps for his country, has featured in three of England's four games during the qualifying campaign, although he has only started one of those matches.
Southgate will now be awaiting an update on Grealish's fitness before he decides whether to call up a replacement.
Man City, meanwhile, will head into the international break as the league leaders after beginning their title defence with four consecutive victories.
They will return to action on September 16 when they travel to the London Stadium for a meeting with Europa Conference League winners West Ham United.