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One week after losing starting running back Raheem Mostert to a season-ending knee injury, the San Francisco 49ers and their revamped backfield will take on the Philadelphia Eagles on Sunday at Lincoln Financial Field. Rookies Elijah Mitchell and Trey Sermon, second-year pro JaMycal Hasty and veteran Kerryon Johnson are set to carry the load for the 49ers after the loss of Mostert. In last week's victory over Detroit, Mitchell, a sixth-round pick from Louisiana, rushed for a game-high 104 yards and one touchdown. On Sunday, the 49ers will face a Philadelphia defense that allowed Atlanta to run for 124 yards and average 4.8 yards per rush last week.

Kickoff is at 1 p.m. ET. San Francisco is a three-point favorite in the latest 49ers vs. Eagles odds from Caesars Sportsbook while the over/under for total points scored is 49. Before you lock in any Eagles vs. 49ers picks and predictions, make sure to check out what the SportsLine Computer Projection Model has to say.

The model, which simulates every NFL game 10,000 times, is up almost $7,900 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 2 of the 2021 season on an incredible 121-79 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 zeroed in on 49ers vs. Eagles and locked in another confident against-the-spread pick. You can only see the model's 49ers vs. Eagles pick at SportsLine. Here are several NFL Week 2 odds and betting lines for Eagles vs. 49ers:

  • Eagles vs. 49ers spread: San Francisco -3 
  • Eagles vs. 49ers Over-Under: 49 points 
  • Eagles vs. 49ers money line: San Francisco -160, Philadelphia +140 
  • SF: WR Deebo Samuel ranked second in the NFL in receiving yards (189) after Week 1
  • PHI: DT Jason Hargrave was tied for second in the league in sacks (two) after Week 1
Featured Game | Philadelphia Eagles vs. San Francisco 49ers

Why the 49ers can cover

One season after playing just two games because of injury, Nick Bosa already looks like the player who was named the NFL's Defensive Rookie of the Year in 2019. In last week's season opener, the edge-rushing attack man constantly found himself in the Lions' backfield, including on a fourth-and-short early in the game. He was credited with three tackles for loss, including one sack.

In addition, quarterback Jimmy Garoppolo is coming off a solid performance. Despite being involved in a quarterback competition with first-round pick Trey Lance all preseason, Garoppolo completed 17-of-25 passes for 314 yards and a touchdown. Most importantly, he did not throw an interception.

Why the Eagles can cover

Jalen Hurts is coming off his best passing performance as a pro. In the win over the Falcons, the second-year quarterback had a passer rating of 126.4 after going 27-of-35 for 264 yards and three touchdowns. That's the highest passer rating by an Eagle since Carson Wentz had a 128.3 rating in Week 5 of 2017.

In addition, Philadelphia has an all-purpose threat in Miles Sanders. The third-year running back from Penn State led the Eagles with 113 scrimmage yards (74 rush, 39 receiving) last week. He is tied for the third most scrimmage yards per touch among running backs since 2019 (minimum 300 touches), behind only Austin Ekeler (6.2) and Christian McCaffrey (6.0).

How to make 49ers vs. Eagles picks

Now, the model has broken down Eagles vs. 49ers from every angle. The model is leaning under on the point total, but it also says one side of the Eagles vs. 49ers spread has all the value. You can only see the model's pick at SportsLine

So who wins 49ers vs. Eagles? And what side on the spread has all of the value? Visit SportsLine now to see which side of the Eagles vs. 49ers spread you should jump on, all from the advanced model that is up almost $7,900, and find out.