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The Denver Broncos (2-1) and San Francisco 49ers (3-0) will clash in Week 4 of the NFL season this afternoon. Kickoff is set for 4:25 p.m. ET from Levi's Stadium in Santa Clara, Calif. The game will broadcast live on CBS.
The 49ers are 3-point favorites over the Broncos on the spread, with the over/under set at 47.5 total points. San Francisco is a -148 moneyline favorite to win outright, while Denver is a +124 underdog to pull off the upset.
Let's get into my Broncos vs 49ers predictions and NFL picks for Sunday, October 4.
My Broncos vs 49ers Prediction
- Broncos vs 49ers pick: Broncos +3 (-120)
My Broncos vs. 49ers best bet is Denver to cover the spread (+3), with the best price currently available at DraftKings. Make sure to find the best odds by checking our live NFL odds page.
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Broncos vs 49ers Odds
| Broncos Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
+3 -120 | 47.5 -110o / -110u | +124 |
| 49ers Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
-3 +100 | 47.5 -110o / -110u | -148 |
Broncos vs 49ers NFL Week 4 Preview
Denver Broncos Betting Preview: Think Twice Before Fading Bo Nix
The Broncos appear to be undervalued road underdogs in this matchup.
The Broncos have a remarkably clean injury report entering this game. There were some concerns with star wide receiver Jaylen Waddle, who was spotted in a walking boot after the Rams game, but he ended up logging full practices.
Bo Nix is the most profitable quarterback in the NFL when faded by the public: since 2024, in the 20 games where the opposing team received the majority of ticket support, Nix is 14-6 against the spread (ATS).
Nix and this Broncos team consistently find ways to keep games close and cover numbers late.
San Francisco 49ers Betting Preview: Numbers Inflated by Easy Schedule
The 49ers hold the No. 1 dropback success rate in the NFL (64%), but their stats are likely inflated by a cupcake schedule (Cardinals, Dolphins, and a jet-lagged Rams squad in Australia).
San Francisco has yet to play a true road game or face a healthy defense. Now, with Nick Bosa sidelined, the 49ers lose their primary pass-rush engine.
Historically, teams covering by 10+ points per game through three weeks are just 47-72 (39%) ATS in their next game over the last 15 years.
Broncos vs 49ers Prediction, Betting Analysis
San Francisco is arguably the most overvalued team in the league right now, and it is currently operating as a public trap with 59% of tickets backing them.
Without Nick Bosa there to disrupt Bo Nix's timing, Denver's defense should be able to do enough to keep this game within a field goal.
I'll grab the +3 with the healthier road underdog.
Pick: Broncos +3 (-120)
