Wales international George North has been ruled out of action for up to four weeks following a knee injury.
North, who recently signed a national dual contract with the Welsh Rugby Union already missed the autumn internationals for Warren Gatland's side due to a similar injury but now races against time to be fit for the Six Nations opener against Scotland.
"George North sustained an injury to his knee during Saints' defeat to Harlequins on Saturday at Twickenham which will require up to four weeks' rehabilitation," Northampton said in a statement."
The 25-year-old sustained the injury first in October while he was playing for his club Northampton Saints in the European Champions Cup but returned to action after a 11-week break during the recently concluded Aviva Premiership clash against Harlequins.
North, who replaced Ahsee Tuala in the 23rd minute had to leave the field in the 64th minute during the game which was won by the Quins 50-21.
Northampton's recently-appointed technical coaching consultant Alan Gaffney added: "While it is disappointing that George will be missing ahead of Saturday's game, this injury means an opportunity for another player in the squad to step up to the plate.
"I'm sure George will be diligent in his rehab, and we all wish him a swift recovery."
Wales head coach Warren Gatland is already without injured British and Irish Lions Sam Warburton and Jonathan Davies for all of Wales' Six Nations campaign while Taulupe Faletau, Dan Lydiate and Hallam Amos are also nursing injuries.