England star Marcus Smith has been ruled out of Harlequins ' Gallagher Premiership clash with Northampton Saints on Monday after returning a positive Covid-19 test.
More than 70,000 people are set to be in attendance at Twickenham for the post-Christmas blockbuster.
It would have been the perfect stage for 22-year-old fly-half Smith to once again demonstrate his talents after impressing in an England shirt last month.
He was one of the star players in England's autumn internationals, as head coach Eddie Jones experimented with some new faces ahead of the upcoming Six Nations.
But Smith and team-mate James Chisholm have both been ruled out of the 'Big Game', after testing positive for the virus on a PCR test earlier this week.
The good news for Harlequins, however, is that they should be available for the following game away at Gloucester in the New Year.
A club statement read: "Due to health and welfare regulations all players must observe a clear graded return to match intensity fitness following a positive Covid-19 result before returning to match action.
"Unfortunately, there was not enough time for either player to pass through these protocols before Big Game 13, and are therefore unavailable for selection for this fixture.
"Both are expected fit for the Club’s Gallagher Premiership fixture away to Gloucester on January 2."
Replacing Smith in the number 10 jersey for Quins will be Will Edwards, who filled that shirt admirably against London Wasps when the former was away with England last month.
There is also another separate late change to the Harlequins side, with Viliami Taulani taking over the number 20 shirt from Dino Lamb for the December 27 clash.
Meanwhile, Joe Marler and Will Collier have been recalled to the front row, preferred ahead of Santiago Garcia Botta and Simon Kerrod.
Saints are boosted by the returns of Dan Biggar and Sam Matavesi, while Juarno Augustus will also come in to join England internationals Lewis Ludlam and Courtney Lawes in the back row.
Harlequins come into the game in poor form, having lost their last two Gallagher Premiership games.
Saints, however, have won their last two but do not travel well – they have only tasted victory once away from home since September.
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