Southgate deployed a 4-2-3-1 system in Sunday's slender 1-0 victory over Serbia, with John Stones recovering from illness to partner Marc Guehi in central defence and help the Three Lions keep a clean sheet.
Both players are expected to continue in the back four alongside full-backs Kyle Walker and Kieran Trippier; the latter suffered with cramp towards the end of the win over Serbia, but he should be fit to start at left-back ahead of Luke Shaw, who has not played since February due to injury.
The most eye-catching selection in Southgate's first XI from matchday one was that of Trent Alexander-Arnold playing in midfield alongside Declan Rice. The Liverpool man could be given another chance to prove his worth from the off, but he faces competition from the likes of Conor Gallagher and Kobbie Mainoo to keep his starting spot.
Phil Foden struggled to make the desired impact on the left wing against Serbia and drifted inside on countless occasions to try and put his stamp on the match. The Manchester City star would prefer to operate in the number 10 role or on the right flank, but midfield sensation Jude Bellingham - the match-winner against Serbia - is expected to continue in an advanced central role, with Bukayo Saka playing on the right.
Southgate is therefore likely to stick with Foden on the left or opt for a change in personnel and hand either Anthony Gordon, Cole Palmer or Eberechi Eze a start, while captain Harry Kane should lead the line once again, despite enduring a quiet outing against Serbia.
England possible starting lineup: Pickford; Walker, Stones, Guehi, Trippier; Alexander-Arnold, Rice; Saka, Bellingham, Foden; Kane