The hosting manager might have been tempted to start with three central defenders in order to quell the threat of Robert Lewandowski, but the Bayern Munich man has been ruled out of this encounter due to a knee problem, so his absence could sway Southgate's decision to stick with a 4-3-3.
Nick Pope became the first ever goalkeeper to keep six clean sheets in his first six starts for England at the weekend and will hope to make that seven here, and he will be offered good protection as close friends John Stones and Harry Maguire reprise their roles in defence.
Reece James and Ben Chilwell will hope to come into Southgate's thinking for starts here, but the latter is unlikely to force his way into the team over an in-form Luke Shaw, while Kyle Walker could also reprise his role in defence after a clean sheet against Albania.
Southgate's decision to start both Declan Rice and Kalvin Phillips against Albania drew criticism from supporters, but it was a move that paid off and England could stick with their two holding midfielders here, despite pressure from James Ward-Prowse.
Mason Mount produced another inspired showing at the weekend and topped off his impressive display with the game's second goal, so he is in no position to relinquish his spot in the middle of the park, as long as he shakes off an injury concern in time to feature.
Harry Kane scored one and set up the other against Albania, and another goal on Wednesday would see him become only the third player ever to score on all seven days of the week for England - a feat previously achieved by Wayne Rooney and Frank Lampard.
England possible starting lineup:
Pope; Walker, Stones, Maguire, Shaw; Rice, Phillips, Mount; Sterling, Kane, Foden