The San Francisco 49ers and the Denver Broncos will face off on Sunday Night Football at Empower Field in Mile High. We've been waiting all day to show you our NFL odds series and deliver a 49ers-Broncos prediction and pick for Sunday night.

The 49ers are coming off a 27-7 rout of the Seattle Seahawks. Unfortunately, the win cost them quarterback Trey Lance, who broke his ankle and is out for the season. Jimmy Garoppolo came into the game and completed 13 of his 21 passes for 154 yards, one touchdown, and no interceptions. Meanwhile, Jeff Wilson rushed 18 times for 84 yards, while Deebo Samuel rushed four times for 53 yards. Samuel also caught five passes for 44 yards, while Brandon Aiyuk had five catches for 73 yards. 

The Broncos defeated the Houston Texans 16-9 last weekend. However, Russell Wilson struggled, completing 14 of his 31 passes for 219 yards, a touchdown, and an interception. Javonte Williams rushed 15 times for 75 yards, while Melvin Gordon rushed 10 times for 47 yards. ‘

The 49ers have won three of the last four games in the matchup, with the series tied at 7-7 overall. The Broncos demolished the 49ers 42-17 in the previous game in this stadium in 2014. Additionally, it was the same game where Peyton Manning broke the all-time touchdown record (before Drew Brees later broke it). The 49ers won their last overall matchup in 2018 by a 20-14 score. Alternatively, the only relevant players left from that matchup that will play this Sunday include Wilson, George Kittle, and Tim Patrick. Yes, Kittle will make his season debut after missing the first two games of the season. 

Here are the 49ers-Broncos NFL odds, courtesy of FanDuel. 

NFL Odds: 49ers-Broncos Odds

San Francisco 49ers: -1.5 (-114)

Live and breathe sports?

🚨 Get viral graphics, memes, rumors and trending sports news delivered right to your inbox with the Clutch Newsletter.

Denver Broncos: +1.5 (-106)

Over: 43.5 (-114)

Under: 43.5 (-106)

Why The 49ers Could Cover The Spread

The 49ers are favorites because they demolished Seattle. However, they have their issues. The 49ers must figure out how to properly use Garoppolo now that he is fully healthy. Will Garoppolo produce, or will defenses line eight in the box because he cannot throw deep?

The first key to winning this game will be the ground attack. Wilson is solid, but the 49ers must also try out options behind him that do not include Samuel. Instead, Jordan Mason should see a few snaps and spell Wilson. San Francisco has options at running back and should not rely heavily on Samuel. However, Samuel continues to produce, catching seven passes for 58 yards and rushing 12 times for 105 yards and a touchdown through two games. Aiyuk has caught seven passes for 103 yards and is still looking for his first touchdown. 

Kittle's return is the main story. In the last matchup with Denver, Kittle went off for seven catches for 210 yards and a touchdown. Can he pull off the same feat in this showdown? Regardless, Kittle is capable of taking control of a game by himself. The 49ers look to work him in slowly and focus more on his blocking. 

The defense continues to roll, and Nick Bosa is off to a great start. So far, Bosa has eight solo tackles and three sacks through two games. He will look to continue his success against a Broncos' line that has not gelled well yet. 

The 49ers will cover the spread if they can run the ball efficiently and put pressure on Wilson. Likewise, they cannot allow Denver to sack Garoppolo, or it will be a long night. 

Why The Broncos Could Cover The Spread

Wilson has plenty of experience facing Kyle Shanahan's 49ers. Wilson is 16-4 lifetime against the 49ers. Additionally, he has a career passer rating of 100.2 with 4,169 yards, 36 touchdowns, and 10 interceptions through 20 games. Last season, he completed 16 of his 23 passes for 149 yards and two touchdowns in the road win over the 49ers. Then, he completed 30 of his 37 passes for 231 yards, two touchdowns, and an interception in the home win against San Francisco. 

Williams has 22 carries for 118 yards but has not found the endzone yet. Thus, he will search for his first against a tough run defense that does not allow much space. Courtland Sutton played in the last game against the 49ers but produced nonexistent numbers (one catch and no yards). Now, he looks to make an impact, especially with Jerry Jeudy possibly missing this week's contest. 

Bradley Chubb remains a threat on defense as he has produced four tackles and two sacks. Chubb must pressure Garoppolo to prevent the 49ers' offense from finding its groove. 

The defense must put the 49ers into 3rd and long situations to amplify its chances of winning. The Broncos will cover the spread if Wilson finds his open receivers, and they can get an efficient running game going. Also, they must stop the rushing attack. 

Final 49ers-Broncos Prediction & Pick

This game may get ugly. The 49ers are a great team, but this is a tough test. They could win this one on a field goal, which would still be enough to cover this little spread. 

Final 49ers-Broncos Prediction & Pick: San Francisco 49ers: -1.5 (-114)