Wales wing George North has suffered another knee injury and will be sidelined for up to a month.
It means that North, who only returned to action last Saturday following an 11-week absence because of knee trouble, faces a race to be fit for Wales' Six Nations opener against Scotland on 3 February.
"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."
North suffered a knee injury while on European Champions Cup duty in October, which ruled him out of Wales' four autumn Tests.
His latest setback, which came after he went on as a replacement against Quins, means he is set to miss Saints' Aviva Premiership clash against Gloucester on Saturday, plus Champions Cup appointments with Clermont Auvergne and Saracens.
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.
Number eight Taulupe Faletau, meanwhile, is another injury absentee who is unlikely to be fit before March, and both flanker Dan Lydiate and wing Hallam Amos suffered injuries last weekend.
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."
North, who has scored 30 tries in 69 Tests for his country, will leave Northampton at the end of this season to join one of Wales' four professional regions - Cardiff Blues, Ospreys, Dragons or Scarlets.