James Ward-Prowse and Ben Chilwell have earned late call-ups to replace their injured compatriots, and it would not be a surprise to see both men start as Southgate takes next week's clash with Hungary into consideration.
Jordan Pickford may be given the night off in goal as Aaron Ramsdale hopes to be rewarded for his impressive Arsenal performances with his first cap, while John Stones and Tyrone Mings could start in defence as Fikayo Tomori is kept waiting.
Chilwell has not played much football this term but could get the nod over Luke Shaw given the Manchester United man's recent fitness issues, while Kyle Walker will miss the Hungary clash if he is booked so may warm the bench as Kieran Trippier earns a start.
Bukayo Saka and Jesse Lingard both put in man-of-the-match displays in last month's thrashing of Andorra, and the former is a strong contender to start on the right, but Lingard may just lose out to Phil Foden on the left.
Amid reported concern over Harry Kane's injury woes being exacerbated by the Andorran pitch, Southgate could elect to bring in the in-form Tammy Abraham to lead the line, but Ollie Watkins will also hope to come into contention for a place.
England possible starting lineup: Ramsdale; Trippier, Stones, Mings, Chilwell; Henderson, Ward-Prowse, Mount; Saka, Abraham, Foden body check tags ::