The San Francisco 49ers (1-0) hit the road to match up against the New Orleans Saints (0-1) at Caesars Superdome on Sunday, September 14, 2025. Date: Sept. 14

Kickoff from Caesars Superdome is set for 1 p.m. ET. San Francisco is a 3-point favorite in the latest 49ers vs. Saints odds from SportsLine consensus, while the over/under for total points scored is set at 40.5. Before making any Saints vs. 49ers picks, make sure you check out the NFL picks from the SportsLine Projection Model.

Learn which TV channel or how to live stream the NFL Week 2 New Orleans Saints and San Francisco 49ers game, Sunday, Sept. 14.

The San Francisco 49ers will be without their quarterback in Week 2 vs. the New Orleans Saints, but signs on their star RB are good.

The 49ers enter Sunday’s game in New Orleans seeking to open a season with back-to-back road wins like in 2019, ’21 and ’23.

The San Francisco 49ers roster moves ahead of Week 2 didn't include the addition of a practice squad WR, which may be good news for an injured player.

Run all they want, this game will still fall on Spencer Rattler's shoulders. He and the Saints passing game must make more plays to beat the 49ers:

The most significant injury for the 49ers is to their franchise quarterback, Brock Purdy. He’s expected to miss several games due to a turf toe-related ailment, forcing the team to turn to Mac Jones to run the offense for the time being. Jones was listed with a knee injury at practice this week but remained a full participant.

The San Francisco 49ers and New Orleans Saints will meet on Sunday. Here's what fantasy owners should do with their 49ers in Week 2.