Joe Gomez suffered a serious knee injury in England training on Wednesday morning
The Liverpool defender is set for a sustained spell on the sidelines after the incident but scans have yet to reveal the extent of the damage done.
Liverpool boss Jurgen Klopp, already without Virgil van Dijk for the season, is now facing up to potentially losing his other first-choice centre-back.
And all signs point towards a long-term injury for Gomez, similar to the cruciate ligament injury he sustained in 2015 after collapsing in pain with no other player around him.
England goalkeeper Nick Pope revealed Gomez played a pass in training before attempting to move, ending up on the deck in distress.
"Joe made a pass or movement with nobody around him and ended up on the floor and was obviously in a great deal of pain," said Pope.
"To see Joe go through something like that and see how much pain he was in wasn't easy for me or any of the lads."
England boss Southgate insisted that seeing an injury like that suffered by Gomez is “one of the worst things" that can happen to an international manager."
The England head coach said: "You are borrowing players and something happens on your watch.
"You feel a responsibility and you start to go back but in this instance there is just nothing we would have done differently.
"What was upsetting was to see him in a fair bit of pain. There was nobody around him when it happened and I didn’t like that element of it. We’ve got to wait for the scan."