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The defending NFC champions, the San Francisco 49ers, might be in crisis mode entering their Week 4 matchup at home against the New England Patriots. San Francisco (1-2) has been without key offensive weapons, including star running back Christian McCaffrey, and lost two consecutive road games, including to the Rams last week, 27-24. New England (1-2) fell at the Jets last Thursday, 24-3, in its most recent contest. The 49ers won the last matchup between the two teams, 33-6, in October 2020.

Kickoff from Levi's Stadium is set for 4:05 p.m. ET. San Francisco is a 10.5-point favorite in the latest 49ers vs. Patriots odds, per SportsLine consensus, while the over/under for total points is 42. Before making any Patriots vs. 49ers picks, you need to see the NFL predictions and betting advice from the proven computer model at SportsLine.

The model, which simulates every NFL game 10,000 times, is up well over $7,000 for $100 players on top-rated NFL picks since its inception. The model enters Week 4 of the 2024 NFL season on an incredible 188-130 run on top-rated NFL picks that dates back to the 2017 season. It is also on a 42-22 roll on top-rated NFL picks since Week 7 of 2022.

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

Now, the model has set its sights on Patriots vs. 49ers and just locked in its picks and NFL Week 4 predictions. You can head to SportsLine now to see the model's picks. Here are several NFL odds and betting lines for spreadmoney line and over/under:

  • 49ers vs. Patriots spread: 49ers -10.5
  • 49ers vs. Patriots over/under: 42 points
  • 49ers vs. Patriots money line: 49ers -595, Patriots +438
  • 49ers vs. Patriots picks: See picks at SportsLine

Why the Patriots can cover

Can the Patriots pull another shocking road upset early in the season? In Week 1, they defeated the Bengals 16-10 despite being a 7.5-point underdog. With the 49ers having struggled of late, they might not have turned things in time for this matchup, especially being without several key pieces on offense and defense.

New England will likely have to lean on their rushing attack led by Rhamondre Stevenson. Despite a dud in Week 3 against the Jets, Stevenson rushed for a combined 201 yards and two scores in Weeks 1-2 combined. He will be leaned on heavily when the game is close with the gameplan likely to be keeping San Francisco's high-powered offense off the field. See which team to pick here.

Why the 49ers can cover

Even without wide receiver Deebo Samuel, tight end George Kittle and star running back Christian McCaffrey, the 49ers looked to be in full control last week in Los Angeles. But they squandered a 24-14 lead in the fourth quarter, falling to the Rams as the offense couldn't make a big play down the stretch. Quarterback Brock Purdy played very well though, throwing for 292 yards and three touchdowns in the defeat.

In the absence of Samuel and Kittle, WR Jauan Jennings joined Brandon Aiyuk in the starting lineup and torched the Rams' secondary. Jennings caught 11 passes for 175 yards and three touchdowns, nearly singlehandedly leading the 49ers to victory. Against a solid New England secondary, Aiyuk and Jennings will have to make plays in space to help San Francisco's offense. Running back Jordan Mason has also been a pleasant surprise, having rushed for 324 yards and two touchdowns thus far with McCaffrey out. See which team to pick here.

How to make Patriots vs. 49ers picks

The model has simulated New England vs. San Francisco 10,000 times and the results are in. It is leaning Under on the point total, and it also says one side of the spread hits over 50% of the time. You can only see the model's Patriots vs. 49ers pick at SportsLine.

So who wins San Francisco vs. New England on Sunday, and which side of the spread hits over 50% of the time? Visit SportsLine right now to see which side of the Patriots vs. 49ers spread you should be all over Sunday, all from the model on a 188-130 roll on its top-rated NFL picks, and find out.