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The Indianapolis Colts (2-4) travel to California to face the San Francisco 49ers (2-3) on Sunday Night Football.  The Colts have had tremendous success against the 49ers over the years, winning four of the last five matchups. However, Indianapolis is just 2-4 in its last six games on the road against San Francisco. 

Kickoff from Levi's Stadium is set for 8:20 p.m. ET. San Francisco is favored by 3.5-points in the latest Colts vs. 49ers odds from Caesars Sportsbook, while the over-under is 41.5. Before locking in your 49ers vs. Colts picks, make sure you check out the NFL predictions from the red-hot SportsLine Projection Model. 

The model, which simulates every NFL game 10,000 times, is up almost $7,700 for $100 players on top-rated NFL picks since its inception six-plus years ago. It went a sizzling 24-14 on top-rated NFL picks last season, returning more than $800. The model also enters Week 7 of the 2021 season on an incredible 125-85 run on top-rated NFL picks that dates back to the 2017 season.

The model also ranked in the top 10 on NFLPickWatch four of the past five years on straight-up NFL picks and beat more than 94 percent of CBS Sports Football Pick'em players four times during that span. Anyone who has followed it is way up.

Now, the model has simulated Colts vs. 49ers 10,000 times and just revealed its NFL picks and predictions. You can head to SportsLine now to see the model's NFL picks. Now, here are several NFL odds and betting trends for Colts vs. 49ers on SNF:

  • Colts vs. 49ers spread: San Francisco -3.5
  • Colts vs. 49ers over-under: 41.5 points 
  • Colts vs. 49ers money line: San Francisco -175, Indianapolis +150
  • IND: The Colts are 7-2 against the spread in their last nine road games 
  • SF: The under is 5-0 in 49ers' last five games following a bye week 
Featured Game | San Francisco 49ers vs. Indianapolis Colts

Why the Colts can cover

Running back Jonathan Taylor has three straight games with over 100 scrimmage yards. Last week against the Texans, Taylor had 14 carries for 145 yards with two scores. Two weeks prior against the Ravens, Taylor tallied 116 yards on four receptions. He also added 53 yards on the ground.  

Taylor has been a tremendous weapon in the Colts' offense. The 49ers' defense allows 113.3 rushing yards per game and Taylor will look to record his fourth straight game with over 100 scrimmage yards. His dynamic ability to make defenders miss in the open field can give San Francisco problems. Plus, the Colts enter Sunday's showdown having covered the spread in four of their last five games. 

Why the 49ers can cover

Head coach Kyle Shanahan and the 49ers are optimistic that quarterback Jimmy Garoppolo will return from injury. Garoppolo suffered a calf injury against the Seattle Seahawks in Week 4, causing him to miss the following game.

The 49ers have the sixth-ranked total defense and allow 329.8 total yards per game. This unit is led by All-Pro linebacker Fred Warner and defensive end Nick Bosa. Warner leads the 49ers in total tackles with 45, including 29 solo. He has recorded at least nine tackles in four of the five games played. Bosa leads San Francisco with eight tackles for loss and five sacks. The Ohio State product has recorded a sack in four of the team's five games on the year. 

How to make Colts vs. 49ers picks 

SportsLine's model is leaning over on the point total, projecting the teams to combine for 45 points. The model also says one side of the spread hits in well over 50 percent of simulations. You can only see the model's 49ers vs. Colts picks at SportsLine

So who wins 49ers vs. Colts on Sunday Night Football? And which side of the spread hits in well over 50 percent of simulations? Visit SportsLine now to see which side of the 49ers vs. Colts spread to jump on, all from the advanced model that is up over $7,900 on its NFL picks, and find out.