Two-time Premier League Player of the Season, De Bruyne, came off with a groin injury midway through City’s goalless draw with Inter Milan last month and has missed the club’s last seven games in all competitions.
Walker, meanwhile, has been forced to sit out City’s last two matches due to a knee problem and wingers Doku and Grealish are both out with minor knocks.
It leaves Guardiola with a number of selection dilemmas ahead of the weekend’s contest between second-placed City and second-bottom Southampton, though the champions are blessed with strength in depth that most other clubs could only dream of.
Guardiola’s men enter the clash as the overwhelming favourites to secure victory, with 19 points separating the two teams at this early stage of the 2024/25 campaign.
There had been some hopes that some or all of City’s absentees could be in line to make their returns at the Etihad but tomorrow’s match comes too soon for the injured quartet.
Asked whether De Bruyne or Walker could be involved, Guardiola told reporters: ‘No, not yet.’
Pressed for a date on De Bruyne’s possible return, Guardiola replied: ‘I don’t know.
‘Of course, I prefer to have all of the squad with the amount of games but it is what it is.
‘Hopefully he comes back soon but I don’t know yet. I would like to tell you but I don’t know.’
On Doku and Grealish’s chances of featuring, the Spaniard bluntly responded: ‘No.’
Despite Southampton’s lowly position in the table, Guardiola has great admiration for Russell Martin and believes his opposite number will enjoy success if he sticks to his principles.
‘He will have success. When this happens, always you have success sooner or later,’ the Catalan added.
‘You just have to change a lot your ideas or your thoughts. Normally, when you change your ideas or your thoughts, I’m not saying to adjust something, it’s not about playing four at the back or five at the back. That is not my point.
‘If you start to change your thoughts for the results then the players will notice. They will know you are not a big believer.
‘When this happens, sooner or later the bad results are coming. They’re coming so always we have bad results. Wolves, look what happened, how we struggled to win.
‘Against Brentford, against Manchester United for half an hour, against Leicester, the starts were really, really good so they have good moments.’
Phil Foden scored his second goal of the season in all competitions as City ran out 5-0 winners over Sparta Prague in midweek.
After the victory, the forward said he felt like he was returning to his best after suffering ‘burnout’ from a gruelling 2023/24 season.
‘I’m not concerned at all because I know when he’s fine that he will get it. He’s a natural talent and he will get it,’ Guardiola continued.
‘The first goal against Sparta Prague… Phil is an incredible talent to solve the game for himself.
‘Phil already has many, many years and you have bumps up and down a little bit. You have to reduce these short setbacks as quickly as possible.
‘They are human beings so let’s be patient and let them feel that in these kinds of moments we are there and everything is going well.
‘I’m happy to hear that he feels good because in the end it depends on himself.’