Winger Jack Nowell will miss England's Six Nations decider against Italy and the rest of the autumn internationals.
Nowell is to undergo surgery on a toe injury that he has been carrying since Exeter's Champions Cup semi-final win over Toulouse last month.
The 27-year-old has not trained for a fortnight and fought through the pain to play in Exeter's Champions Cup and Premiership final victories.
"I've ruptured all the ligaments around my toe," Nowell said.
"I've been strapped up for the last two weeks and have had to dig deep."
England visit Italy on Saturday in their final game of the delayed Six Nations, a point behind leaders Ireland.
Eddie Jones' side then face Georgia, Ireland and Wales in the pool stages of the Autumn Nations Cup in November before a final game against a yet unnamed opponent on 6 December.
Nowell missed the opening stages of last year's World Cup after being injured in Exeter's 2019 Premiership final loss to Saracens.
"It's a relatively long-termish injury, not like a knee reconstruction, but it's relatively long term," added Exeter boss Rob Baxter.
"You've got to give him great credit for deciding that he wanted to really drive these last few weeks of his club season."