Saints boss Chris Boyd has confirmed that lock David Ribbans is likely to be out for the rest of the season after undergoing ankle surgery.
But there is better news on another key second row forward, with Courtney Lawes set to be fit in time for the Challenge Cup quarter-final at Clermont Auvergne on March 31.
Both players will definitely miss Friday's east midlands derby against Leicester Tigers at Welford Road, with Api Ratuniyarawa, Alex Moon, James Craig and Alex Coles vying for starting spots.
Ribbans has not played since Saints' Gallagher Premiership defeat at Saracens on Allianz Park at March 2.
He was named in the team to face Bristol Bears a week later but was forced to withdraw in the build-up to the game.
And having been assessed, it was decided that he would require an operation to rectify the problem.
"David had an operation on his ankle yesterday or the day before and he's going to be lucky to play again this season," said Boyd at Wednesday's media session.
"It will depend on how he recovers, but that's probably unfortunately for him and for us season-ending."
Lawes suffered a calf strain during England's Six Nations defeat to Wales in Cardiff on February 23.
But he is now nearing a return to action.
"Courtney won't play on Friday - he's probably a week away so hopefully he'll be ready to play against Clermont in the Challenge Cup quarter-final next Sunday. He may or may not get in for that," Boyd said.
"But given the importance of his year, we certainly won't be rushing him back.
"But if he's ready we'd certainly welcome him."
Dylan Hartley has been out of action since playing in Saints' win at Worcester Warriors on December 21.
But Boyd expects the England hooker, who has been suffering with a knee injury, to play some part before the end of the season.
"Dylan had a specialist appointment yesterday and it was actually really positive," Boyd said.
"There's only six rounds of the Premiership remaining and that's spread over nine or 10 weeks so I'd expect Dylan to play some rugby for us before the end of the season."
Luther Burrell took a heavy hit early on against Saracens last Sunday and is now going through concussion protocols, ruling him out of this week's game at Leicester.
"He took a pretty nasty bang," Boyd said.
"He hasn't got a big history of concussions but he managed to take a fairly hefty knock on the swede so he's on concussion protocols.
"He won't make the weekend."
But Dan Biggar will be back to face Tigers after helping Wales to secure a Six Nations Grand Slam.
"Jimmy Grayson has done a great job in his absence but Dan's a seasoned international," Boyd said.
"He holds a very pivotal role in that Welsh side that's done so well in the past 14 or 15 games.
"He is pivotal for us, too.
"He's a fierce competitor, a good footballer, a good student of the game so we certainly welcome him back."