49ers vs. Broncos Best Bet: Back San Francisco in Week 4
Denver Broncos vs. San Francisco 49ers (-2.5): Total set at 48.5
The San Francisco 49ers have been an absolute machine to start the year, cruising to an undefeated 3-0 record while showing the league what tremendous offensive efficiency looks like. The 49ers lead the NFL in that category by a wide margin, as Brock Purdy has his unit firing on all cylinders and putting up points at will.
Meanwhile, the Denver Broncos breathed a massive sigh of relief last week. After starting sluggishly and dropping into an early 16-0 hole, Bo Nix led the Broncos to a second-half comeback victory (30-26) over the Los Angeles Rams on Sunday Night Football.
So, will Denver build off those second-half heroics this week out on the road, or will San Francisco’s top-ranked attack systematically pick them apart at Levi’s Stadium?
Let’s see whether the advanced numbers reveal any betting edge. Check the live NFL odds for the latest line.
Denver vs San Francisco Breakdown
Denver Offense vs San Francisco Defense
Denver Offense
| EPA/play | Dropback EPA | Rush EPA | Success Rate | Dropback SR | Rush SR | |
| Last Week | 0.005 | 0.002 | 0.009 | 38.5% | 41% | 34.6% |
| Season | -0.063 | -0.048 | -0.087 | 40.8% | 43.9% | 35.8% |
San Francisco Defense
| EPA/play | Dropback EPA | Rush EPA | Success Rate | Dropback SR | Rush SR | |
| Last Week | 0.148 | 0.232 | -0.015 | 51.8% | 50% | 55.2% |
| Season | -0.009 | 0.071 | -0.122 | 45.9% | 43.3% | 49.4% |
Denver’s offense has struggled mightily to find its footing this season, currently ranking 22nd in overall EPA/play and 25th in success rate. Outside of an explosive second-half surge against the Rams last week, Bo Nix and the Broncos have struggled to move the ball consistently, sitting in the mid-20s across almost every major statistical category.
That’s not ideal when you know you’ll likely need to score touchdowns, not field goals, against this Niners team that averages 32.7 points per game.
So while last week’s comeback effort allowed Broncos OC Davis Webb to take a breath after getting nothing but criticism through two weeks, it’s tough to believe everything is now fixed. The Broncos had one good half of football that they desperately needed at home. I’m not sure that any of it carries over to this week’s road game.
However, Denver will have opportunities, as the San Francisco defense has functioned as a middle-of-the-pack unit, which is all they really need given the offensive numbers the team has put up.
The 49ers rank 16th in opponent EPA/play (-0.009), but they allowed 0.148 EPA/play and a high 55.2% rush success rate a week ago in their 36-30 win over Arizona. With a few more minutes on the clock, the Cardinals may have even come back to win.
So, as praiseworthy as the 49ers’ offense has been this season, this team might be a loss or two away from exposing its defensive flaws to the whole league. Stopping the run remains the biggest leak in San Francisco’s defense, but how effectively the Broncos’ rushing attack exploits that flaw remains to be seen.
San Francisco Offense vs Denver Defense
San Francisco Offense
| EPA/play | Dropback EPA | Rush EPA | Success Rate | Dropback SR | Rush SR | |
| Last Week | 0.455 | 0.841 | -0.089 | 56.6% | 61.3% | 50% |
| Season | 0.330 | 0.622 | -0.050 | 56% | 64.2% | 45.2% |
Denver Defense
| EPA/play | Dropback EPA | Rush EPA | Success Rate | Dropback SR | Rush SR | |
| Last Week | -0.000 | 0.021 | -0.057 | 40.5% | 42.6% | 34.8% |
| Season | 0.023 | -0.028 | 0.107 | 41.9% | 42.7% | 40.5% |
San Francisco’s offense is an absolute juggernaut right now, ranking first in the league in overall EPA/play and success rate. Brock Purdy is building an early MVP case, leading the NFL in dropback EPA for two straight weeks and capping it off with a massive 0.841 dropback EPA last week.
Those numbers have made scoring easy for San Fran, as they also lead the league in red-zone touchdown conversion rate at 90%. But if they can get their running game on better footing soon (-0.050 season rush EPA), this team will establish itself as the league’s most lethal. And with Christian McCaffrey still in the 49ers’ backfield, it’s easy to believe that San Francisco’s running game numbers will be on the rise.
So the task for this Denver defense, still searching for its elite form from a year ago, is figuring out how to contain the 49ers for 60 minutes at the very least. Force them into red-zone field goals to stay within striking distance. That’s the kind of play Broncos backers have to expect if they want to believe they can win.
The numbers and signs are there for the Broncos defense, too. The prospects on paper aren’t near the top of the league like they were in 2025, but Denver’s also faced three very good QBs through the first month of the season. Coming out with a 2-1 record after facing Patrick Mahomes, Trevor Lawrence, and Matthew Stafford, while your own offense is only averaging 20 points per game, is quite the accomplishment for Denver’s defense.
But the schedule doesn’t get any softer for top teams in the NFL, and without more support from Bo Nix and company, you’ve got to wonder how long this Broncos defense can hold up. Two of those three QBs are former MVPs in this league, and Purdy is the early-season favorite in 2026 without question.
I’m not sure I’d bet on Denver games right now expecting this Broncos defense to keep shouldering the load. They can’t wait around for Bo Nix to possibly get hot in the second half, and if the Rams had scored touchdowns instead of field goals while building that first-half lead, I don’t believe the Broncos would have shown nearly as much life in the second half.
Holding the 49ers’ attack in the same fashion has to be the top goal for the Broncos defense this week, but finding the same success on the road will be a lot tougher.
Injuries and Roster Notes
Denver Broncos
- Jaylen Waddle – WR | Probable
- K. Dobbins – RB | Probable
- Marvin Mims Jr. – WR | Probable
- Dondrea Tillman – LB | Questionable
San Francisco 49ers
- Nick Bosa – DE | Out
- Mike Evans – WR | Questionable
- Trent Williams – OL | Questionable
- Dre Greenlaw – LB | Questionable
- Keion White – DE | Questionable
Denver vs San Francisco Best Bet
Best Bet: San Francisco -2.5
Even if the Broncos find ways to hold the 49ers to field goals when they can, plenty of game scripts suggest 17 points for San Francisco could still cover this spread. That’s how rough Denver’s offense has been for most of the season, and that still assumes San Fran scores only 17 or 20 points. I think they’ll blow past that range in this one.
The 90% red-zone TD rate is impressive, but it’s the EPA/play numbers San Francisco has put up this year that have been astonishing. There is no way I could do anything but back this type of offense at home, with the spread where it is. Purdy’s dropback EPA numbers are through the roof right now, but in Kyle Shanahan’s system, with Shanahan calling the plays, the scheme and the player deserve credit for those stats.
Even against a Broncos defense as respected as this one, I don’t imagine Shanahan’s offense is anything less than a B+ version of itself. That’s still probably good enough to beat the Broncos by two scores unless Denver’s offense ultimately does find a way to clone that second half vs. the Rams for the full 60 minutes here.
I just don’t see it happening.
Lay it with the 49ers.
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