The San Francisco 49ers are trying to rebuild confidence as they head to SoFi Stadium for a Week 2 NFL Preseason matchup against the Los Angeles Chargers on Sunday night. After losing to the Chiefs in Super Bowl LIV, the injury-ravaged Niners went 6-10 last season, and quarterback Jimmy Garoppolo will try to redeem himself. He was injured much of last season, but was also ineffective, so he will be looking over his shoulder at rookie Trey Lance. Garoppolo won three of the six games he started in 2020, while Lance went 17-0 in his college career at North Dakota State. The Chargers, who were 7-9 last season, are resting most of their top players as new coach Brandon Staley builds up depth and gives his rookies plenty of work.

Kickoff is set for 7:30 p.m. ET in Inglewood, Calif. San Francisco is listed as a six-point favorite in the latest 49ers vs. Chargers odds from Caesars Sportsbook, up a half-point from the opener, while the over-under for total points scored is 34. Before making any Chargers vs. 49ers picks, be sure to see the NFL predictions and betting advice from SportsLine's Tom Fornelli

The CBS national writer went a profitable 31-22 last season on his NFL best bets. What's more, he has demonstrated a particularly sharp eye for the 49ers. In fact, Fornelli has gone a stunning 14-6 on NFL picks involving San Francisco. Anyone who has followed him is way up.

Now, Hunt has set his sights on 49ers vs. Chargers and recently revealed his expert NFL picks and analysis. You can head to SportsLine now to see his picks. Here are the NFL lines and betting trends for Chargers vs. 49ers:

  • 49ers vs. Chargers spread: 49ers -6
  • 49ers vs. Chargers over-under: 34 points
  • 49ers vs. Chargers money line: 49ers -245, Chargers +205
  • SF: San Francisco was 3-0 against the spread as a road favorite in 2020
  • LAC: Los Angeles went 5-2 ATS as an underdog last season
Featured Game | Los Angeles Chargers vs. San Francisco 49ers

Why the 49ers can cover

San Francisco will have a clear advantage with the Chargers opting to let many starters skip the preseason. Garoppolo and Lance will be eager to show their worth and could push the ball downfield. Lance threw an 80-yard touchdown pass in last week's 19-16 loss to the Chiefs and Garoppolo completed all three of his passes on his only series.

The Niners piled up 383 yards, averaging almost six per play, and while Lance completed only five of 14 passes, he saw numerous on-target passes dropped. The 49ers also ran for 175 yards against Kansas City.

The running back battle will give an edge to San Francisco, with at least four quality runners in a fierce battle to be the backups to presumed starter Raheem Mostert. JaMycal Hasty ran for 63 yards on nine carries last week, while Wayne Gallman and Trey Sermon combined for 47 yards. Receivers Nsimba Webster and Jajuan Jennings also showed their playmaking ability, adding 53 yards on three runs. Second-year wideout Brandon Aiyuk, who has been the star in workouts, could also make an impact this week with more playing time.

Why the Chargers can cover

Los Angeles stars like Herbert, receiver Keenan Allen and running back Austin Ekeler are preparing via workouts and scrimmages, so veteran Chase Daniel will run the offense. He threw for 104 yards in last week's 13-6 win against the Rams, while Easton Stick completed all seven of his passes for 63 yards. Tight end Donald Parham, the likely backup to Jared Cook, had 31 yards on just two catches. The running game is likely to get a lot of work after putting up 112 yards in the opener. Larry Rountree, a sixth-round pick out of Missouri, had 63 on nine carries.

The Chargers' defense was intense in the teams' joint practices this week and it is likely to cause havoc Sunday night. The 49ers' offensive line is banged up, and Lance was running for his life for most of his time in the opener. San Francisco yielded five sacks, with Lance going down four times, and turned the ball over twice. The Chargers spent a lot of time in the Niners' backfield in scrimmages this week and come off a game in which they held the Rams under 200 yards.

How to make Chargers vs. 49ers picks

Fornelli has analyzed this matchup from all angles, and he is leaning under on the point total. He also has discovered a critical X-factor that has him jumping all over one side of the spread. He's only sharing what it is and his expert Niners vs. Chargers picks at SportsLine.

So who wins Niners vs. Chargers? And which critical X-factor makes one side of the spread a must-back? Visit SportsLine now to see Tom Fornelli's 49ers vs. Chargers pick, all from the NFL expert who's 14-6 on picks involving San Francisco, and find out.