49ers vs. Broncos prediction: MVP favorite Brock Purdy and San Francisco look to stay undef

What you need to know ahead of these teams facing off on Sunday

Oct 3, 2026 at 11:48 am ET • 3 min read

The Denver Broncos and San Francisco 49ers are facing off on CBS this Sunday at 4:25 p.m. ET at Levi's Stadium. Both teams are coming off wins, with Denver at 2-1, while the 49ers are one of the two undefeated NFC teams at 3-0. 

The 49ers started the season strong, defeating the Rams, who were a Super Bowl favorite heading into the season. They then defeated the Miami Dolphins and, most recently, took down the Arizona Cardinals.

Denver began the year with a 31-10 divisional loss to the Kansas City Chiefs, then beat the Jacksonville Jaguars and the Los Angeles Rams.

The Niners have been hit hard by injuries, which we'll get into more below, but they've shown they can adapt and win with whoever is on the field. Their offense is a fun one to watch — remember the hook-and-ladder that allowed for Deebo Samuel to have a stat line of 0 receptions for 80 yards and a touchdown?

The Broncos have demonstrated that they can come from behind and win, as they did last week against the Rams.

Where to watch 49ers vs. Broncos

Date: Sunday, Oct. 4 | Time: 4:25 p.m. ET
Location: Levi's Stadium (Santa Clara, CA)
TV: CBS | Stream: Paramount+
Follow: CBS Sports App
Odds: 49ers -3 (via DraftKings)

49ers vs. Broncos injuries

To say the Niners have been hit hard by injuries is an understatement. Wide receivers Ricky Pearsall, Demarcus Robinson, Christian Kirk and De'Zhaun Stribling; tight end Jake Tonges; running back Isaac Guerendo; offensive linemen Austen Pleasants and Brett Toth; defensive ends Sam Okuayinonu, Mikail Kamara and Andrew Farmer II; defensive tackles Alfred Collins and CJ West; linebacker Nick Martin; defensive back Darrick Forrest and cornerback Nate Hobbs, to name a few, have all been on the injured reserve or PUP list.

There are so many players injured that the team has to strategically pick who they put on injured reserve so they don't run out of space, and that brings us to this week's injury report. They had 10 players on Wednesday's report, including Mykel Williams, who began the season on the PUP list. Defensive lineman Nick Bosa was listed with a knee/calf injury and is expected to miss multiple weeks. He is not on IR likely because the team doesn't have the space.

Wide receivers Mike Evans (ribs) and KhaDarel Hodge (knee); linebacker Dre Greenlaw (quad); and defensive linemen James Thompson Jr. (ankle) and Keion White (hamstring) were all listed as non-participants in Wednesday and Thursday's practice. Running back Christian McCaffrey and tackle Trent Williams also did not practice on Wednesday, but were listed as "not injury related/resting player," and both returned as limited participants on Thursday.

49ers vs. Broncos need to know

MVPurdy: Let's pretend it's not too soon to start talking about who the MVP will be and instead talk about why the 49ers quarterback is off to an MVP start. The definition of who the MVP is varies across the league and among fans every year, whether you think it's for the player who performed best overall or who meant the most to their team. Whichever way you slice it, Mr. Irrelevant, if we can still call him that, is in the conversation. He ranks eighth in passing yards (789), is tied for first in touchdown passes (9), second in completion percentage among current starters (72.3) and third in yards per attempt (10.2). He hasn't been sacked yet, and the challenge for the Broncos' defense is that it isn't quick to get to the QB. Denver's secondary is tough and can force turnovers, but the 49ers are quick to give the ball up.

The run game: The 49ers offense excels in the run game, and the Broncos defense doesn't excel in stopping the run. San Fran is sixth in rushing yards (409) and fourth in yards per carry (5.1). Denver's defense has allowed the third most yards (431) and is tied for the second-most yards per carry (5.1). Denver will need to even up this mismatch as much as possible, or the Niners will run all over them (pun intended). The Broncos' run game is not their offensive strong suit, with the second-fewest rushing yards (243) and the second-most fumbles (2). The Niners' run defense is in the middle of the pack. Who can establish the run, and who can establish it early, will be huge in the outcome of this game.

49ers vs. Broncos prediction

The 49ers haven't given me a reason to believe they won't win this game, and while I think it will be competitive, I think they improve to 4-0. They have made it work with the number of injuries they're dealing with, but if the injury bug doesn't slow down soon, the holes will become more obvious than they are now.