Mako Vunipola will miss England's New Zealand tour and Saturday's Aviva Premiership final after undergoing knee surgery.
The 23-year-old dislocated the patella in his right knee in Saracens' 23-6 Heineken Cup final defeat to Toulon in Cardiff last weekend, the club have confirmed.
England's second set of tourists fly out to New Zealand on Monday, after Saturday's Premiership final between Saracens and Northampton.
Vunipola's knee problem further deepens England's injury concerns at loosehead prop, with Joe Marler suffering a hip complaint.
England called up Bath's Nathan Catt as late cover for Marler in the initial group of tourists that flew out to New Zealand on Tuesday.
Wasps' three-cap loosehead Matt Mullan will now start England's first Test against the All Blacks in Auckland on June 7 unless Marler makes a rapid recovery.
Head coach Stuart Lancaster received more positive news from Northampton, with hooker Dylan Hartley fit enough to take a seat on the Saints bench for the Premiership final.
The 28-year-old has not played for two months with shoulder trouble, and his return indicates he will be ready to fly out to New Zealand on Monday.
Saints prop Alex Corbisiero will not tour this summer having only just recovered from long-term knee trouble, and Leicester hooker Tom Youngs has been handed compassionate leave while his wife receives treatment for an illness.
England must compete in the first Test with the All Blacks without their Premiership final contingent, leaving as many as 15 players unavailable.
The International Rugby Board scheduled all summer series to start just seven days after the Premiership final owing to a technicality of ruling the May 31-June 1 weekend as the official first weekend of June.
Had the IRB deemed June 7-8 the official first weekend of the month, England's Test series against the All Blacks would not have kicked off until June 14.