The severity of Strief's injury was not immediately known.
A source said it's possible that Strief could be healthy enough to return from injured reserve after the minimum eight weeks, but that is still undetermined.
The good news for New Orleans is that veteran left tackle Terron Armstead appears set to return from his own long-term shoulder injury after the Week 5 bye. Armstead, who had surgery in June, returned to practice on a limited basis last week.
Rookie first-round draft pick Ryan Ramczyk, who has now started two games at left tackle and two games at right tackle, can settle in as Strief's long-term replacement.
Head coach Sean Payton and offensive line coach Dan Roushar both credited Ramczyk for his poise and development during the first quarter of the season.
"It's been good," Payton said. "He's smart and has played on both sides [of the line]. It's been very encouraging, and there is a toughness and a mental toughness about him. I'm pleased and glad we have him."
Strief suffered a sprained MCL in his knee in Week 1. Then he returned to the lineup in Week 4 against the Miami Dolphins in London before suffering another knee injury. It's unclear if it was a recurrence of the same issue or something more significant.
Strief, 34, is tied with Drew Brees as the two longest-tenured players on the team. He arrived as part of New Orleans' remarkable 2006 draft class as a seventh-round draft pick out of Northwestern in the same year that Payton and Brees arrived.
Strief has started 94 games in his 12-year career. And his 2016 season was arguably one of the two or three best of his career. He allowed only two or 2.5 sacks in 16 games, depending on the statistical service. According to Pro Football Focus, Strief didn't allow a sack against Von Miller, Khalil Mack, Vic Beasley, Jason Pierre-Paul or Cliff Avril, among others. The Saints rewarded Strief with a rare raise this offseason, worth at least $700,000 and more in per-game bonuses, even though he still had two years left on his deal.
The Saints' offensive line also had to deal with some offseason turbulence when center Max Unger missed several months because of foot surgery, but he returned during the preseason and has started every game this year.