Anthony Watson suffered a broken jaw in England training on Wednesday and is unlikely to feature for his country again this year.
The winger, 22, joins Sam Jones in having sustained a serious setback while training, with the uncapped Wasps flanker breaking his right fibula on Monday.
Watson's club side Bath confirmed the injury on Thursday as England prepare for matches against South Africa, Fiji, Argentina and Australia across November and December.
"Anthony Watson broke his jaw in the England training camp earlier this week," said director of rugby Todd Blackadder.
"It's too early for a full medical prognosis on how long he'll be out for, but it's likely he'll miss the autumn Internationals.
"He's in great hands with our medical team and we look forward to seeing him back on the pitch when he's ready."
It is a blow for head coach Eddie Jones as he seeks to maintain his 100 per cent winning record at the England helm, having completed an unprecedented whitewash in Australia in June.
Watson has scored 12 tries in 24 Tests.