England centre Manu Tuilagi has been ruled out of Saturday's Test against South Africa after suffering a groin strain.
Tuilagi's space among the replacements will be taken by Chris Ashton.
England's injury crisis showed no signs of abating with Tuilagi the latest to be ruled out of their November internationals opener against the Springboks.
Tuilagi was set to appear for England for the first time since 2016 after an injury-dogged two years. But his troublesome groin played up again in training Thursday.
"Lads have seen him around, spoken to him," England co-captain Owen Farrell said. "He seems in high enough spirits and I don't think it's too serious. But with his history, it's not one to risk. I'm sure he'll be back in the next couple of weeks."
England are confident Tuilagi will be fit for their match next weekend against New Zealand. A source described the injury as "low, low grade" and that Tuilagi would have played against South Africa had it been a World Cup final. He will re-join the squad on Sunday.
Tuilagi's misfortune means Ashton is back in the England mix having last played for the national side in 2014. Ashton has played just one match this season for Sale Sharks having completed a close-season move. He missed the start of the campaign through suspension.