Breida re-injured his left ankle this past Sunday during pregame warmups prior to a 43-16 loss at Seattle.
49ers coach Kyle Shanahan confirmed Breidas status on Monday after the running back had just five carries for six yards and three catches for 51 yards vs. the Seahawks.
Breida has rushed for 744 yards and ranking third in the league with an average of 5.64 yards per carry.
With Breida unavailable, undrafted rookie Jeff Wilson is expected to start.
"He hits the hole and he runs hard," Shanahan said of Wilson. "He's a very good zone runner. He doesn't mess around. He sets his track. When he sees an open gap, he puts his foot down and goes for it."
Wilson had 61 yards on 15 carries and also caught eight passes for 73 yards vs. the Seahawks.
"Jeff played very well,´ Shanahan said. "He earned that last week how he played, but it got stronger, especially with what happened with Breida in pregame warmups. We were going to give Jeff a lot anyways, but we knew Breida struggled in pregame. Then it got worse as the game went. Jeff also got hurt in the game too. He had to leave and go to the locker room for a little bit. But, it was good to see him. We all know he played well, but it was good to see him bounce back and play through some stuff that was bothering him also."
On a positive note, speedy wide receiver Marquise Goodwin could return this week after missing the last two games for family reasons.
Shanahan is hoping that despite his team's 2-10 record, it can put up a better fight against the 6-6 Broncos than it did vs. the now 7-5 Seahawks.
"We didn't play very well," Shanahan said. "That doesn't go into they didn't respond to my challenge. You have to play very good football to win games and we haven't done that enough consistently in all three phases throughout the year. Magic words don't make people different. I want people to focus and worry about what they can control. We have four games left. We know we're eliminated from the playoffs. So is this year over? This year has everything to do, for me, about next year."
--RB Matt Breida will not play Sunday vs. the Denver Broncos. Breida re-injured his left ankle this past Sunday during pregame warmups prior to a 43-16 loss at Seattle. 49ers coach Kyle Shanahan confirmed Breidas status on Monday after the running back had just five carries for six yards and three catches for 51 yards vs. the Seahawks.
--LB Dekoda Watson will be placed on IR with a torn calf muscle.
--S Jaquiski Tartt will miss this week's game with a stinger.
--WR Marquise Goodwin could return this week after missing the last two games for family reasons.