"He's going to require season-ending surgery, unfortunately," Fisher said. "Our doctors agreed with the second opinion, and so it will take place in the next couple of days."
The Rams placed Saffold on injured reserve, which means he will miss the rest of the season.
Saffold is scheduled for surgery with Dr. Frank Cordasco from the Hospital for Special Surgery in New York, according to ESPN NFL Insider Adam Caplan. Cordasco repaired Saffold's left shoulder in January.
In addition, Fisher announced tight end Lance Kendricks had surgery Monday to repair a torn ligament in his finger. He had been playing with the injury since Week 1.
Kendricks isn't expected to be out long, but Fisher indicated he could be questionable for the team's next game against Cleveland on Oct. 25. Tight end Justice Cunningham was promoted from the practice squad to take Saffold's spot on the roster.
Veteran Garrett Reynolds will step into one of the starting spots at guard in Saffold's place. With Saffold out, Reynolds instantly becomes the team's most experienced starting lineman. He's played 57 games at right tackle and both guard spots since entering the league in 2009.
Saffold also had offseason surgery on his left shoulder after suffering a similar injury -- and continuing to play with it -- last season.
The Rams and Saffold, after getting a second opinion, decided it was best not to again play through the injury. With the projected recovery time, the Rams believe Saffold will be back to 100 percent around February or March.
"Once we got both opinions together, he was willing to try to play, but inevitably it's going to come out again when you're talking about the condition of the shoulder," Fisher said. "So we just felt like for career-wise, future-wise, it's best to get it fixed. He fought through it with the left shoulder last year, and we fixed it when the season was over. So we're getting an earlier start."
Saffold's latest injury adds to a growing list of ailments since coming to the NFL in 2010. He's only twice played a full season, and the Oakland Raiders called off a free-agent contract with him in the 2014 offseason after he failed a physical because of left shoulder concerns.
After the Oakland deal fell apart, the Rams wound up re-signing Saffold to a five-year, incentive-laden deal worth up to $42.5 million. His $4.5 million base salary for 2016 becomes guaranteed on March 11. Additionally, the Rams still have $3 million of Saffold's original $5 million signing bonus scheduled to count against the cap in $1 million increments over the next three years.
Running back Trey Watts was signed to the practice squad in Cunningham's place.