Manchester City manager Pep Guardiola has confirmed both Jack Grealish and Jeremy Doku are set for a spell on the sidelines.
Neither Grealish nor Doku were part of City's squad for their 5-0 victory over Sparta Prague in the Champions League on Wednesday, along with absentees Kevin De Bruyne and Kyle Walker.
After the match, Guardiola explained that both are struggling with injuries, and he was unsure exactly when they will be available again.
"Hopefully Jack will be maybe one week, 10 days, Jeremy a little longer," Guardiola told a press conference.
Alongside long-term injured players Rodri and Oscar Bobb, this gives City yet more unwelcome news.
On a more positive note, while Guardiola was delighted with striker Erling Haaland after his goals in midweek, he was also full of praise for winger Savinho, who got the assist for the Norwegian's first goal.
"He's playing really good, he's a winger who can play on both sides… being just three months with us, his level is really, really, really high," Guardiola said.
"I want to say something; it's thanks to the work of Míchel at Girona – he has done it."
Under pressure Southampton manager Russell Martin, meanwhile, has the unenviable task of taking his out-of-form team away to the champions.
The Saints were beaten 3-2 at home by Leicester City last weekend, having initially gone two goals up, and Martin appealed to the fans to keep supporting the team.
"The fans have been brilliant since I've been here," he told BBC Sport.
"I'm not sure the boos were directed at their team because the team were giving everything. My message is to be really supportive, they've been great."
Given Southampton's slow start to the season, there have been questions about whether Martin is the right man to keep the club in the Premier League, though the manager himself would not be drawn on such speculation.
"I've nothing to say apart from that I need to keep working, and we need to win a game of football," he said.
"I hope they [the fans] will always turn up and support their team. They've been amazing."
PLAYERS TO WATCH
Manchester City - Erling Haaland
Among players to play over 500 minutes against promoted teams, Haaland has the second-best minutes-per-goal ratio (one every 60 minutes - 13 goals in 780 minutes) in Premier League history.
He is currently on a three-game goal drought in the league, which is just the second time this has happened, though he did score two against Sparta Prague in the Champions League on Wednesday.
Southampton - Tyler Dibling
Tyler Dibling has scored one league goal this season and created seven chances for his team-mates - the third-most in the Southampton squad.
But the 18-year-old's best skill is his ball carrying, having accrued the second-furthest distance (1,124m) of any Saints player. He has had eight dribbles that have ended in a shot, which is a club-leading stat.
MATCH PREDICTION: MANCHESTER CITY WIN
In-form City are currently second in the Premier League table after accumulating 20 points from their opening eight matches, while they are the only team in the division yet to lose.
Since losing three consecutive Premier League home games against Southampton between 2001 and 2004, City are unbeaten in their last 12 against them at the Etihad Stadium (W10 D2).
The Citizens are currently on their longest-ever unbeaten league run, with their 2-1 victory over Wolves last time out extending it to 31 matches (W25 D6), since defeat at Aston Villa last December.
The previous meeting between these teams finished 4-1 to City in April 2023, which means that Southampton have won just one of their last 13 (D3 L10) Premier League meetings with them.
The omens, then, are not great for second-bottom Southampton. They have lost seven of their eight Premier League games this season, drawing the other against Ipswich Town in September. It is just the second time the Saints have ever failed to win their opening eight matches of a league campaign, after 1998-99 (first nine).
Only Mick McCarthy (zero) has ever won fewer points than Martin in their opening eight Premier League matches as a manager.
OPTA WIN PROBABILITY
Manchester City - 79.6%
Draw - 11.9%
Southampton - 8.6%