Coach Sean Payton revealed after the game that Brees is set to undergo an MRI and X-rays to determine the severity of the injury.
"He took a heavy shot in the first half. As he came out in the second half, he felt it was really impacting him," Payton told reporters. "So, specifically, he'll get an MRI and X-Rays. His back felt sore. As he tried to throw, he just came up to me and said, 'Hey, I don't feel like I'm capable of playing.' And so, quickly, we made the switch and, you know, that happens sometimes.
"He felt strong enough about letting me know and I know when he does that, which is probably gonna be the first time in 15 years, that it was significant enough where he felt like he couldn't function in the second half."
Brees' availability for Week 11 against the Atlanta Falcons is unclear at this point.
The injury occurred after the veteran quarterback was sacked by 49ers defensive end Kentavius Street midway through the second quarter as he looked to make a play downfield. Street was flagged for roughing the passer on the play.
Brees finished out the half, but appeared to be in some discomfort following the hit. He completed eight of 13 pass attempts for 76 yards and a touchdown prior to exiting.
"I was not going to be able to be effective," Brees said of the injury. "It had nothing to do with pain. It was simply just what my body was going to be able to do or not be able to do."
When the Saints took the field to begin the second half, Brees, still suited up with his helmet on, remained on the sidelines as Jameis Winston took over. The team announced shortly thereafter that Brees was questionable to return. He would sit out for the remainder.
Winston proved to be a capable fill-in as the former starter completed six of 10 pass attempts for 63 yards. Taysom Hill, who saw snaps at QB in certain packages prior to Brees' injury, took a few more under center, but did not attempt a pass. He finished with eight carries for 45 yards and two fumbles (one lost).