The Denver Broncos (2-1) head to Levi’s Stadium on Sunday to take on the unbeaten San Francisco 49ers (3-0) in one of Week 4’s marquee matchups. Denver has knocked off the Jaguars and the Rams the last two weeks after a Week 1 loss in Kansas City, while San Francisco has opened the season with victories over the Rams, the Dolphins, and the Cardinals. The 49ers have been one of the NFL’s most explosive teams through three weeks, averaging 32.7 points per game, while the Broncos have relied on timely defensive plays and fourth-quarter execution.
As mentioned, the Broncos are coming off a dramatic 30-26 victory over the Rams on Sunday Night Football. Denver trailed 16-0 at halftime before mounting a furious second-half comeback behind quarterback Bo Nix and a defense led by Talanoa Hufanga. Hufanga returned an interception 66 yards for a touchdown and later sealed the game with a second interception in the closing seconds. Nix threw two touchdown passes and scored the game-winning touchdown on a one-yard sneak with 47 seconds remaining as the Broncos erased a double-digit deficit for the second consecutive week. Meanwhile, San Francisco survived a tougher-than-expected challenge from Arizona, defeating the Cardinals 36-30. Quarterback Brock Purdy threw four touchdown passes, including two scoring strikes to George Kittle, while Christian McCaffrey added 116 total yards and a touchdown. The 49ers overcame injuries to Mike Evans and Trent Williams and held off a late Arizona rally to improve to 3-0.
Quarterback play will be a major focus entering Sunday. Nix has thrown for 605 yards with four touchdowns and three interceptions through three games while continuing to show an ability to direct Sean Payton’s offense. His poise during the comeback win over Los Angeles was one of the biggest reasons Denver escaped with the victory. On the opposite sideline, Purdy has been one of the NFL’s hottest quarterbacks, throwing for 789 yards, nine touchdowns, and just one interception. He has completed more than 72 percent of his passes, and the 49ers have yet to allow a sack this season. San Francisco’s offense has been nearly unstoppable, thanks to the combination of Purdy, McCaffrey, Kittle, and Deebo Samuel.
The biggest storyline is whether Denver’s defense can slow that high-powered offense of the 49ers that currently ranks among the league’s best in both efficiency and scoring. To do so, the Broncos must generate pressure on Purdy, something no opponent has done through three games. Purdy has yet to be sacked this season. Assuming the 49ers can score, another key storyline is whether Nix can keep pace. If Denver can turn the game into a defensive battle, it has a chance to pull off the upset. If Purdy continues his MVP-caliber start and the 49ers maintain their offensive rhythm, San Francisco will be in a strong position to move to 4-0
Let’s dive into the numbers and see if we can’t find an additional sweat or two.
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Game Details and How to Watch: Broncos vs. 49ers
- Date: Sunday, October 4, 2026
- Time: 4:25PM ET
- Site: Levi’s Stadium
- City: Santa Clara, CA
- TV/Streaming: CBS
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Latest Game Odds: Broncos vs. 49ers
The latest odds as of Friday courtesy of DraftKings:
- Moneyline: Denver Broncos (+124), San Francisco 49ers (-148)
- Spread: 49ers -3
- Total: 47.5
The Total opened at 46.5, and the Spread has climbed a half point after opening San Francisco -2.5.
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Rotoworld Bet Best Bets
Expert picks & predictions for Broncos vs. 49ers
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Our model calculates projections around each moneyline, spread and over/under bet for every game on the NFL calendar based on data points like past performance, player matchups, betting trends, and weather forecasts.
Once the model is finished running, we put its projection next to the latest betting lines for the game to arrive at a relative confidence level for each wager.
Here are the best bets our model is projecting for Sunday’s game between the 49ers and the Broncos:
- Moneyline: NBC Sports is recommending a play on the 49ers on the Moneyline
- Spread: NBC Sports is leaning towards a play on the 49ers -3.
- Total: NBC Sports is leaning towards a play on the Total OVER 47.5.
The single most important factor in this game is how unstoppable the 49ers’ offense has been through three weeks. San Francisco is averaging 263.0 passing yards and 136.3 rushing yards per game, and Brock Purdy has been surgical — 789 passing yards, nine touchdowns, and one interception at a 133.1 passer rating. The 49ers convert 63% on third down and 90% in the red zone, both the best marks in the league, and no other team is above 58% or 89% respectively.
The season-long numbers from 2025 back up how legitimate this unit is. San Francisco ranked 1st in third-down conversion rate (50.72%), 3rd in completion percentage (69.34%), 4th in passing touchdowns (1.94 per game), 7th in passing yards (263.47 per game), and 10th in points scored (25.71 per game). They were 4th in sack rate allowed (4.7%) and 9th in yards per pass attempt (7.52). That’s an offense that protects its quarterback and finishes drives. Against a Denver defense that has allowed 431 rushing yards at 5.1 yards per carry this season, the 49ers’ ground game should have a field day.
Key Mismatch: the Broncos’ inability to stop the run vs. the 49ers’ success toting the rock. Denver has allowed 431 rushing yards at 5.1 yards per carry through three games, and San Francisco runs at 5.1 yards per carry themselves. That obviously favors the 49ers and Christian McCaffrey. The season-long numbers support the ledger leaning to San Francisco. Denver ranked 2nd in rushing yards allowed (91.06 per game) and 3rd in yards per carry allowed (3.87) last season, but those numbers have cratered in 2026. The Broncos also ranked 31st in third-down conversion rate defense (33.76%) and 23rd in fourth-down conversion rate defense (51.85%) last season — they struggle to get off the field in situational football. That’s the key to the Over. San Francisco is going to sustain drives, convert on third down, and finish in the red zone. Against a Denver defense that can’t stop the run and struggles on third down, the 49ers should put up points.
Broncos vs. 49ers: Betting Trends and Stats
- The Broncos are 2-1 against the spread this season
- The 49ers are 2-1 against the spread this season
- Denver is 1-2 to the OVER this season
- San Francisco is 2-1 to the OVER this season
Quarterback matchup: Broncos vs. 49ers
- Denver: Bo Nix
2026 Statistics: 3GP, 605 Passing Yards, 4 TDs, 3 INTs, 80.3 RTG, Sacked 5 times - San Francisco: Brock Purdy
2026 Statistics: 3GP, 789 Passing Yards, 9 TDs, 1 INT, 133.1 RTG, Sacked 0 times
Broncos vs. 49ers: Top Playmakers
Broncos
- RB J.K. Dobbins
2026 Statistics: 3GP, 35 carries for 121 Yds, 0 TDs / 1 reception on 2 targets for 4 Yds, 0 TDs - WR Jaylen Waddle
2026 Statistics: 3GP, 11 receptions on 20 targets for 150 Yds, 0 TDs / 1 carry for 14 Yds, 0 TDs - WR Pat Bryant
2026 Statistics: 3GP, 6 receptions on 9 targets for 86 Yds, 1 TDs / 1 carry for 16 Yds, 0 TDs
49ers
- TE George Kittle
2026 Statistics: 3GP, 12 receptions on 16 targets for 174 Yds, 3 TDs - RB Christian McCaffrey
2026 Statistics: 3GP, 35 carries for 166 Yds, 3 TDs / 13 receptions on 17 targets for 104 Yds, 0 TDs - WR Deebo Samuel Sr.
2026 Statistics: 3GP, 9 receptions on 11 targets for 159 Yds, 2 TDs / 4 carries for 30 Yds, 0 TDs
Broncos vs. 49ers: Injury Update
Broncos
- LB Dondrea Tillman (hamstring) is listed as questionable for Sunday’s game
49ers
- WR Mike Evans (ribs) is listed as questionable for Sunday’s game
- LT Trent Williams (neck) is listed as questionable for Sunday’s game
- DE Keion White (undisclosed) is listed as questionable for Sunday’s game
- DE Nick Bosa (calf) is listed as OUT for Sunday’s game
- LB Dre Greenlaw (quad) is listed as questionable for Sunday’s game
- DE Romello Height (undisclosed) is listed as questionable for Sunday’s game
- DT James Thompson Jr. (ankle) is listed as OUT for Sunday’s game
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