Rising star Maro Itoje has joined a growing injury list on Monday after becoming the latest England player to be ruled out of the end-of-year internationals.
The 21-year-old fractured his right hand during Saracens' victory over Welsh side Scarlets at Allianz Park in the European Champions Cup on Saturday.
North London club Saracens said Itoje, the European player of the year, will require surgery and be sidelined for at least six weeks.
That will rule him out of England's upcoming internationals against South Africa, Fiji, Argentina and Australia at Twickenham, starting with the match against the Springboks on November 12.
"For any team to lose a player of the ability of Maro is a blow, and he will be missed through the autumn for both Saracens and England," said Saracens director of rugby Mark McCall in a statement.
"What's now important for Maro is his recovery, and we look forward to his return later this season."
Itoje's absence is yet another setback for England coach Eddie Jones, who is due to name his squad on Wednesday.
The Australian, who has won all nine of his Tests since taking charge of England, was already without Itoje's Saracens and England second-row partner George Kruis, James Haskell, Anthony Watson and Jack Clifford because of injury.
Itoje went off early in the second half of Saracens' 44-26 win over the Scarlets after his arm was trapped awkwardly as he made a tackle.
He has become a key figure in the England set-up since Jones took over following the hosts' first-round exit at last year's World Cup.
Itoje had a central role as England won the Six Nations with a Grand Slam and starred again in the team's 3-0 series success in Australia.
He also helped Saracens complete an English Premiership and European Champions Cup double last season.
With Itoje and Kruis now out of action, Jones may revert to recalling the experienced pair of Joe Launchbury and Courtney Lawes to the second row.
Itoje had also been spoken of as a possible England openside flanker given injuries to Haskell, Leicester's Mike Williams and Wasps' Sam Jones.
But it looks as if Jones will now have to select a specialist back-row in that position.