The Three Lions are looking to maintain their perfect start to the Euro qualifiers and already have nine points out of nine after three wins.
England restarted their Euro qualifying campaign on Friday night with a 4-0 win over Malta, though Grealish was left on the bench and Southgate has done it again against North Macedonia.
However, two of his Manchester City teammates were named in the side in John Stones and Kyle Walker.
Jordan Pickford, Luke Shaw, Harry Maguire, Trent Alexander-Arnold, Declan Rice, Jordan Henderson, Bukayo Saka, Harry Kane and Marcus Rashford made up the rest of the side.
But Grealish, who had three days of partying following Manchester City's treble-winning campaign, must make do with another evening in the dugout.
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Several videos emerged of Grealish in party mode after City won the Champions League earlier this month.
Pep Guardiola's men defeated Inter Milan 1-0 in Istanbul, where the squad boozed up until the early hours of the morning.
And Grealish was even spotted at 7am still in his City kit still going strong, singing songs along with Kyle Walker and Erling Haaland.
But the former Aston Villa star did not stop there as the celebrations took him to Ibiza, where he continued his booze cruise.
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Finally, the winger and the rest of the players reunited in Manchester for the open-top bus parade last Monday showing off their Premier League, FA Cup and Champions League trophies.
Once again, Grealish and co were spotted downing drinks before being called up for England duty just days later.
He was joined by Walker, John Stones, Kalvin Phillips and Phil Foden, none of whom started on Friday night against Malta.
The Three Lions have conceded just once so far but the European minnows have proved they have goals in them with budding stars such as Elif Elmas, who won Serie A with Napoli this season.
Southgate had addressed City's England stars on their antics over the week, though insisted everyone is raring to go.
"We are going to have to take it bit by bit and see how they are," he said.
"I spoke to them when they arrived, firstly to say what an incredible achievement. We said we are heading into the unknown, there is no way of knowing individually how they are going to react and respond to what they've been through.
"Everybody is fit. We have got a lot of considerations, particularly the boys who arrived later and are coming off the back of a massive emotional high with the game at the weekend.
"It's always complicated, the decisions you have to make. The team has trained really well, the focus has been excellent.
"I'm always monitoring everything the players do, wherever they are. We are used to dealing with the Champions League scenario. It was more complicated when Tottenham played Liverpool (in 2019) because we were into the Nations League semi-final three days later.
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"We're used to dealing with it, we know our players inside out. Our focus is on the team now. I've said to the players I have to push them. I have to push the players to get the results we need.
"The responsibility lies with them, they have to drive the team and get the performance we want."