Harlequins are likely to be without Mike Brown for the next six to nine months after the full-back was told he requires surgery on his knee.
The club's record appearance holder exacerbated the injury which he initially picked up in preseason in the Champions Cup victory over Bath last weekend.
And now director of rugby is preparing to be without the services of Brown for the rest of the season.
“Losing Mike is a big loss. He's tried hard to train and play over the past few weeks,” boss Paul Gustard said.
“Unfortunately his situation worsened, and it would be damaging to his long-term knee health to try and play.”
“We will look to see how we can use Mike in other capacities to help the squad.”
Praised by teammate Gabriel Ibitoye, 34-year-old Brown is one of the senior figures within the home team dressing room at The Stoop, making over 300 appearances for the club spanning more than a decade.
Harlequins head of medical services, Mike Lancaster added: “Mike has been the model professional and is fully committed to a conservative reload and return to play, within hopefully six to nine months.
“Unfortunately, after playing the last two games, the restriction in function would not allow Mike to perform at his best or indeed allow optimal preparation within the week.”
The injury to Brown leaves Ross Chisholm and summer arrival Travis Ismaiel as the only other options at full-back, with Aaron Morris also on the club's injury list.
The news does carries concern for the Quins backline, which is set to lose Joe Marchant to Super Rugby in February when he joins the Blues on loan.
While the team recently welcomed back experienced scrum-half Danny Care from an ankle injury.
Brown has won 72 caps for England during his career, making him the country's most-capped player at his position.
