George Kruis has been ruled out of England's tour of South Africa by his club boss at Saracens, Mark McCall.
British and Irish Lions lock Kruis is to have surgery on an ankle problem at the end of the European season, meaning he will miss the three-Test series against the Springboks in June.
He will, however, be available for Saracens' bid to win the English title via the Premiership play-offs.
The top four sides at the end of the regular season go forward to two semi-finals, with the winners contesting a Twickenham final for the right to be crowned champions of England.
"He's not going to tour, no," said Saracens rugby director McCall. "He's going to have surgery at the end of the season."
Kruis's absence threatens to leave England coach Eddie Jones without up to six senior players for the South Africa series.
Sunday saw Saracens and England back-row Billy Vunipola emerge unscathed from his first competitive action in three months as his club booked a home semi-final with a 51-14 thrashing of already-relegated London Irish.
Saracens will face either Newcastle or Wasps in the last four.
This was Vunipola's first senior match since breaking his arm in a 15-15 European Champions Cup draw at Opsreys on January 13.
The 25-year-old has not played international rugby union for more than two years, mainly as a result of knee and shoulder injuries.
But the No 8 is now on course to start Saracens' final regular-season Premiership match against Gloucester next weekend as he tries to regain full fitness.
"It's good to get him back on the park," said McCall of powerhouse loose forward Vunipola.
"We'll try to give him as much game time as we can next week, start him I'm sure against Gloucester next weekend, all being well. It's a shame it's a fallow weekend after that."
The former Ireland international added: "He'll be a bit nervous next week, he's only played three games in total this year.
"He's done a hell of a lot of rehab, so it's good to get some of the walking wounded back.
"I don't think anyone sees it, but it was really tough when he broke his arm. He was very emotional straight after that.
"But he just believes that whatever will be will be, things happen for a reason but now he's back and doing what he likes best.
"We've got a training week the week after Gloucester and we'll make that week as tough as it needs to be."
London Irish now face an immediate return to the second-tier Championship, with technical director Declan Kidney determined they don't become a "yo-yo" club.
"Irish are definitely up for the fight, but you don't want to become a yo-yo side," said former Ireland coach Kidney.
"There will be big things learnt this year. It's far from a foregone conclusion that we'll bounce straight back up.
"But it's important now to build really solid foundations so that when we're next back in the Premiership we're more competitive."
British and Irish Lions lock George Kruis, pictured in 2017, is to have surgery on an ankle problem at the end of the European season