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' NatWest 6 Nations opener against Scotland on February 3.
"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."
Wales wing George North will leave Northampton at the end of the season after agreeing a national dual contract with the Welsh Rugby Union, the WRU has announced.
The flying winger was instrumental in securing a 2017/18 European Rugby Champions Cup place for Northampton as his side beat both Connacht Rugby and Stade Francais to claim the final spot in the competition.
The juggernaut wing, who has won 69 Wales caps and scored 30 tries, has agreed a deal from next term, the Welsh Rugby Union announced on its official Twitter feed.
Northampton released their own statement confirming 25-year-old North's departure. It is not known at this stage which of the four Welsh regions he will join.
During North's four-year spell with the Saints, he played 104 times amassing 160 points in the process.
Northampton were wrong to return George North to the field of play following a head injury against Leicester but have escaped any sanction, the Concussion Management Review Group (CMRG) has found.
North was injured in the first half of the Aviva Premiership clash on December 3 but despite appearing to have been knocked unconscious, he passed a head injury assessment and was allowed to resume by Saints' medical staff.
The CMRG set up to investigate the incident concluded that while there was "sufficient evidence" to end North's involvement in the match, the club did not "intentionally ignore the player's best interests".
George North will not play for Northampton again until he has been assessed by an independent expert in head injuries.
The Welsh wing, who has suffered a series of concussions, was cleared by Saints medics to continue playing during Saturday's Aviva Premiership clash with Leicester despite replays suggesting he had been knocked out following a tackle from Adam Thompstone.
Questions have been raised about whether the player's welfare was best served by his return to action but Northampton insist they were fully in compliance with World Rugby's head injury assessment protocols.
The club does admit, however, that the footage available to them at the time was limited and have taken the precautionary steps of withdrawing North from action pending the specialist's verdict.
George North will be out until the end of April after having further tests on a head injury.
The Welshman has now suffered three concussion in recent months and will spend some time on the sidelines.
Wales wing George North will not play for Northampton in Saturday's European Champions Cup quarter-final at Clermont Auvergne after his latest head injury.
North has been knocked unconscious three times in recent months, including in last Friday's 52-30 win over Wasps.
Winger George North says he's feeling OK after being knocked out during Northampton Saints' win over Wasps.
The Welshman suffered a knee to the head by Nathan Hughes, who was sent off for dangerous play but protested his innocence.
North was stretchered off unconscious and in a neck brace, but tweeted to say he was fine.
The Lions captain Sam Warburton has praised Australia for a "thrilling" test match in Brisbane.
"That was entertaining, that's for sure," he said in a pitch side interview with Sky Sports. "The last 20 minutes were so hard and we really had to dig in. Credit to Australia."
George North who scored a try in the first half has praised the travelling fans for "their fantastic support".