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The San Francisco 49ers could get two of their top players back in time for Week 4, which could make bettors reconsider backing them when they make their Week 4 NFL picks. The defending NFC champions have been plagued with early-season injuries, but are expected to have tight end George Kittle back on the field on Sunday to help Brock Purdy air out the offense. Star receiver Deebo Samuel is still questionable to play at home against the New England Patriots and could also return for anyone choosing the 49ers with their NFL predictions.

San Francisco is a 10.5-point favorite in the NFL odds, and bettors may have shied away earlier in the week because of the mounting injuries. Does the potential return of Kittle and Samuel make you rethink backing the 49ers with your Week 4 NFL picks? All of the Week 4 NFL lines are listed below, and SportsLine's advanced computer model has all the NFL betting advice and NFL predictions you need to make the best Week 4 NFL picks now.

The model, which simulates every NFL game 10,000 times, is up well over $7,000 for $100 players on A-rated NFL picks since its inception. The model enters Week 4 of the 2024 NFL season on an incredible 187-130 run on top-rated NFL picks that dates back to the 2017 season. It is also on a 41-22 roll on A-rated NFL picks since Week 7 of the 2022 NFL season.

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, it has turned its attention to the latest Week 4 NFL odds and NFL betting lines on the spread, money line, and over-under, and locked in picks for every NFL matchup. Head here to see every pick.

Top Week 4 NFL predictions

We can tell you one of the model's strongest Week 4 NFL picks is that the Saints (+2.5, 41.5) cover the spread versus the Falcons. New Orleans has done very well in this series, winning 10 of the last 13 meetings against Atlanta. The Saints have also done very well as the road underdog, going 5-1 ATS in their last six games against home favorites.

The Saints offense has been especially effective so far this season, as Derek Carr has completed 68% of his passes while Alvin Kamara has racked up 285 rushing yards with four touchdowns. The Falcons have the 28th-ranked rush defense in the league, so Carr should feel comfortable handing the ball off so the veteran running back can get the Saints into the end zone. See which other teams to pick here.

Another one of its Week 4 NFL betting predictions: the Steelers (-2, 40) cover on the road versus the Colts. Pittsburgh's run defense slowed down Chargers running back J.K. Dobbins last week, holding him to just 44 yards on 15 attempts. They will now face Colts running back Jonathan Taylor, who leads a rushing attack that is averaging 5.4 yards per carry.

Steelers edge-rusher T.J. Watt has 5.5 sacks, four tackles for loss, 15 tackles and two forced fumbles in five career games against the Colts. He had two sacks and two tackles for loss in the most recent meeting (Week 15 of last season) and is on pace to become the second-fastest player to reach 100 career sacks behind Reggie White. SportsLine's model expects Watt to be disruptive again on Sunday, one reason why the Steelers are covering the spread in well over 50% of simulations. See which other teams to pick here.

How to make Week 4 NFL picks

The model has also made the call on who wins and covers in every other game on the Week 4 NFL schedule and just revealed three teams that win outright at least 70% of the time, potentially giving you a huge payday. You can only get every pick for every game at SportsLine.

So what NFL picks can you make with confidence, and which three must-see teams should you lock in now? Check out the latest NFL odds below, then visit SportsLine to see which teams win and cover the spread, all from a proven computer model that has returned well over $7,000, and find out.

Week 4 NFL betting odds, lines, spreads

Get Week 4 NFL picks at SportsLine

Sunday, Sept. 29

Saints at Falcons (-2.5, 41.5)

Bengals at Panthers (+4.5, 47)

Rams at Bears (-3, 40.5)

Vikings at Packers (-3, 44)

Jaguars at Texans (-5.5, 44.5)

Steelers at Colts (+2, 40)

Broncos at Jets (-8, 39.5)

Eagles at Buccaneers (+1, 42)

Commanders at Cardinals (-3.5, 49)

Patriots at 49ers (-10.5, 40.5)

Browns at Raiders (+2.5, 36.5)

Chiefs at Chargers (+7, 41.5)

Bills at Ravens (-2.5, 46.5)

Monday, Sept. 30

Titans at Dolphins (-2.5, 37)

Seahawks at Lions (-3.5, 46.5)