Heinrich Brüssow is set to miss Saints' Aviva Premiership clash with Newcastle Falcons at St James' Park on Saturday evening (kick-off 5.30pm).
The South African flanker was forced off after just 13 minutes in the recent Anglo-Welsh Cup semi-final defeat at Bath.
Brüssow sustained a hamstring injury and has not been training this week.
Interim head coach Alan Dickens said: "Heinrich Brüssow is struggling.
"He came off with a hamstring injury and he hasn't been training this week."
Courtney Lawes will also miss out after being sidelined for the remainder of the season with a knee injury sustained during England's Six Nations defeat to France in Paris.
"It's s shame because Courtney's been one of our stand-out performers this season," Dickens said.
"Week in, week out, he's been fantastic and it's a shame he won't be able to see the last five games out.
"We wish him a speedy recovery.
"Everyone else who has come back from international duty is ready to play."
Teimana Harrison is absent as he serves a one-week ban for his sending off at Bath.
Prop Alex Waller continues to recover from the broken arm he sustained against Newcastle back in December.
"Alex Waller is due to go and see the specialist this week," Dickens said.
"He's training but not rugby training, chucking the ball about.
"He's had a week off as part of his rehab and fingers crossed for good news this week."