Alex Waller's remarkable run of games is set to come to an end after the prop broke his arm in last Friday's defeat to Newcastle Falcons.
Waller was making his 150th consecutive Premiership appearance in that match, but suffered an injury during the second half.
He was forced to have surgery a day later and will now be sidelined for eight to 10 weeks.
"Alex Waller has broken his arm so he will be out for a number of weeks," confirmed Saints boss Jim Mallinder.
"He's been absolutely tremendous and to go 150 games in the Premiership without missing one is fantastic.
"But unfortunately, unless he has a very quick recovery after his operation, which I don't think the surgeons will allow, then that will end his run of games.
"He's such a consistent performer, he will be back soon and we'll look forward to seeing him back in a Northampton shirt."
Waller's absence means Saints will call upon summer recruit Francois van Wyk and Campese Ma'afu to compete for the loosehead spot.
And Mallinder said: "We're still strong in the prop area.
"We've still got Francois van Wyk and Campese Ma'afu, who has come back from international duty with Fiji, so we've got no problems in that area."
Jamal Ford-Robinson can also play loosehead, but he is set to remain on the tighthead side with Kieran Brookes still out with a hand injury.
"Jamal will be competing with Paul Hill for that tighthead role," Mallinder said.
George North, who suffered a knee injury against Saracens in October, is set to miss Saturday's Champions Cup clash with the Ospreys at Franklin's Gardens.
Tom Stephenson (hamstring) and Harry Mallinder (concussion) are also doubtful, but locks David Ribbans and Christian Day are available, and so is Luther Burrell, who suffered concussion in the defeat at Worcester last month.
"I don't think he will," said Mallinder when asked whether North would feature this weekend. "He's out on the field running now, but I don't think he'll be fit to play this weekend.
"Thankfully our second rows are now available so we'll be seeing a change in that area.
"Luther Burrell is fit again, which is good news."