Another Tottenham player, midfielder Dele Alli, has withdrawn from the squad with a minor muscle strain
England striker Harry Kane will be rested for Tuesday's friendly against Switzerland at Leicester City's King Power Stadium with manager Gareth Southgate keen to protect his talisman.
The 25-year-old Tottenham Hotspur forward, who won the Golden Boot at this year's World Cup with six goals, has started 61 matches in all competitions since the start of last season.
"I thought this is a good opportunity to do it," Southgate said on Monday. "Harry falls in the category in which we have several players where we have to watch how much they play."
Southgate could make up to nine changes from the team that started England's Nations League campaign with a 2-1 defeat by Spain at Wembley Stadium on Saturday.
Kane's Spurs team mate Eric Dier will captain a side that is likely to include goalkeeper Jack Butland, defenders James Tarkowski, Kyle Walker and Danny Rose, midfielders Ruben Loftus-Cheek and Fabian Delph, plus striker Danny Welbeck.
"It was a short break with no pre-season and everybody was back earlier than I am sure everybody would have expected for club matches, although that is entirely understandable," Southgate told reporters on Monday.
"We talked a bit after the World Cup about the demands of the modern player. Everybody has got to play a part in that but the clubs own the player and they have got to do the right thing for themselves.
Gareth Southgate has said he is going to rest Harry Kane tonight, leaving Rashford and Welbeck as England's only two strikers! 🏴— Soccer AM (@SoccerAM) September 11, 2018
If YOU were England manager, which other striker would you call-up? 🤔 pic.twitter.com/iQS9SXdTEb
"Normally we have not got opposing objectives and the clubs would be holding their breath and hiding behind their sofas watching our teams go out.
"But this is one of those occasions where what we want to look at with our squad ties in with doing the right thing with the players for our long-term benefit. So I thought this is a good opportunity to do it."
Another Tottenham player, midfielder Dele Alli, has withdrawn from the squad with a minor muscle strain.
Alli, 22, picked up the injury against Spain and is set to return to his club for further treatment. He faces a race to be fit for Saturday's Premier League clash at home to Liverpool though Southgate said he should be ready for that match.
"Alli has just had a minor strain and should be fine for his club at the weekend I would think, but Tuesday's game will come too quickly," he told a pre-match news conference.
England have called up Leicester City duo Ben Chilwell and Demarai Gray from the Under-21s for the Switzerland friendly.
Luke Shaw, who was concussed after a blow to his head in the loss to Spain, returned to his club Manchester United on Monday.
England face the Swiss after three straight defeats and have never lost four consecutive matches.