Having secured qualification for next year's finals in Germany after last month's win at home to Italy, Southgate's concern turned to the missing players and how to adjust the squad.
"You always have to adapt. We'd maybe have written two possible teams for the (next) two games but you never really know what's going to come your way," Southgate said in a press conference on Thursday.
"We have lost more players than is normal and there's some long-term injuries amidst that, which is a big shame for the players themselves, but then there’s always opportunities for the players coming in."
Southgate faces England's final games of the year without key players like Real Madrid's Jude Bellingham and Chelsea's Levi Colwill, both out with shoulder injuries.
The coach added that due to the absences, it is important as a manager to find the balance and be able to make the tough decisions, after he was questioned over the absence of Chelsea striker Raheem Sterling.
"As a player, you never agree with a manager's decision to leave you out, but you just hope you do it in the most respectful way possible, with constructive points so they can go away and work on things," said Southgate.
Southgate also spoke of how, despite England leading Group C with 16 points after six games, his priority is to prove they are a top team that wins games, despite facing constant criticism.
"The most important message revolves around our day-to-day standard on the training ground," said Southgate. "We aspire to be a top team, and we've been consistent for a while, and that comes from everything you do and the things no one else sees."
