The England boss has seen his plans for recent matches disrupted by injuries to Raheem Sterling and Jordan Henderson and has joined Pep Guardiola and Jurgen Klopp in a growing chorus to allow teams to make extra changes during this packed season.
Southgate said: "We were able to make five changes against Belgium – we made four in the end – and clubs don’t have that option.
"What will it take for that to change? There were a couple of less serious injuries against Belgium but what do we do? Wait until we get a load of really nasty ones?"
Southgate appreciates he has a duty to protect players for their clubs and believes England have gone to extra measures to protect the physical condition of the squad.
He said: "I have to be fair to the club managers. They are their players firstly, and they have the right to play them as they see fit. What we have got to do as a collective is to try to help the load.
"We could not have prepared physically any better than we did last week. We have given players extra days’ recovery. We have tapered the training appropriately and we have still ended up with a couple of injuries. So that is a worry in the longer term because with no winter break … something has to give."