The Manchester United left-back saw red for two bookable offences in Thursday's 2-1 success over Italy, incurring one yellow card for time-wasting before scything down Mateo Retegui a minute later.
Thankfully for Southgate, a ready-made replacement in Ben Chilwell is fit and raring to go, and the Chelsea man should immediately be drafted in to cover for Shaw, although Kieran Trippier was picked to shore up the backline in the final 10 minutes on Thursday.
With fewer than 72 hours to recover from their Italian exertions and flights home, Southgate may consider bringing in Reece James as well, but John Stones, Harry Maguire and Jordan Pickford ought to retain their places.
As well as losing Shaw to suspension, England fans witnessed the painful sight of Jude Bellingham limping off the field at the Stadio Diego Armando Maradona, although the severity of the 19-year-old's issue is yet to be determined.
Either way, Jordan Henderson is on hand to cover alongside Declan Rice and Kalvin Phillips, while Bukayo Saka faces little competition for his spot on the right and should start once more.
Having only been given 12 minutes off the bench against Italy before being sacrificed for Trippier, Phil Foden may be given a second bite at the cherry on the left ahead of Jack Grealish, while Harry Kane continues in the number nine role after scoring his record-breaking 54th Three Lions goal.
England possible starting lineup: Pickford; James, Stones, Maguire, Chilwell; Henderson, Phillips, Rice; Saka, Kane, Foden