England Billy Vunipola will miss the All Blacks test next month after breaking his arm for the third time in 12 months.
Vunipola faces another 12-week lay-off after Saracens confirmed that the No 8 fractured his left arm against Glasgow Warriors on Sunday.
The injury, which forced him from the field during the second half of a 13-3 win for the Premiership champions at Scotstoun, will require surgery and is sure to rule him out of England's autumn fixtures against South Africa, Japan, New Zealand and Australia.
To compound matters for Saracens coach Mark McCall, and possibly Eddie Jones, Saracens also revealed that his brother Mako picked up a calf strain. According to Saracens his "progress will be monitored".
And in a third injury blow to Sarries, following a bad-tempered Heineken Champions Cup encounter, Nick Isiekwe suffered an ankle sprain.
He will be assessed by a consultant to determine the length of his recovery.
Billy Vunipola broke his right arm twice last season, once against Ospreys in the Champions Cup in January and again during England's second Test defeat to South Africa in Bloemfontein five months later.
The 25 year-old had endured a torrid 2017 before that, missing the 2017 British and Irish Lions tour to New Zealand to undergo shoulder surgery and then suffering a knee injury that required another operation upon his return.
With Nathan Hughes suspended and facing a disciplinary hearing this week and Sam Simmonds out until 2019 with a knee ligament injury, Jones faces a back-row re-think.
Two possible options to wear the No 8 shirt in November are Bath's Zach Mercer, who was involved in last month's training camp, and Ben Morgan of Gloucester.
Morgan won the last of his 31 caps in England's tournament-ending defeat to Australia at Rugby World Cup 2015.
England's walking wounded | Players unavailable to Eddie Jones
PROP
Mako Vunipola (calf)
Ellis Genge (knee)
Beno Obano (knee)
Matt Mullan (knee)
LOCK
Joe Launchbury (knee)
Jonny Hill (hand)
Nick Isiekwe (ankle)
BACK ROW
Billy Vunipola (arm)
Sam Simmonds (ACL)
Nathan Hughes (expected ban)
Jack Willis (knee)
SCRUM-HALF
Dan Robson (ankle)
CENTRE
Jonathan Joseph (ankle)
Ben Te'o (thigh)
WING
Anthony Watson (Achilles)
Marland Yarde (knee)
... and ...
Joe Marler (prop, retired)