Two NFC foes go at it in Week 2 of the 2025 NFL season as the San Francisco 49ers limp into New Orleans to take on the Saints. The 49ers fight an uphill battle this week as they once again have been bitten by the injury bug. Meanwhile, the Saints are looking to find their footing with their young signal caller. As always, these San Francisco 49ers at New Orleans Saints Preview and Predictions get you set for this matchup.
San Francisco found itself in a slugfest last week during their gritty 17-13 win against the Seattle Seahawks. However, they did not come out of it unscathed. The 49ers lost star tight end George Kittle early with a hamstring injury. On top of that, quarterback Brock Purdy suffered a turf toe during that game. While he was able to finish, he is now week-to-week and will likely sit out this game. This puts former New England Patriots quarterback Mac Jones in line for the start under center. Brandon Aiyuk is already on the shelf and Jauan Jennings is still not practicing. This could be a rough day for the Niners.
New Orleans hung tight last week in its 20-13 loss against the Arizona Cardinals. The Saints offense looked efficient under Spencer Rattler as they out gained the Cards 315-276 in total yards on the day. Their defense also came to play, sacking Kyler Murray five times and holding him to just 163 passing yards on the day. More importantly, they limited the mobile quarterback to just 38 rushing yards. The Saints will enter this game without star safety Julian Blackmon who will undergo surgery for a shoulder injury he suffered last week. Defensive end Chase Young remains out for this game as well. The former 49er missed Week 1 with a calf injury and has yet to return to practice.
San Francisco 49ers at New Orleans Saints Preview and Predictions
Christian McCaffrey Over 81.5 Rushing Yards (-112 via Caesars)
McCaffrey carried a questionable tag with him into the opening week of the season leaving us wondering if he would suit up against the Seahawks. Thankfully for his team he did make the start and ended up gaining 69 yards on 22 carries against Seattle. The star running back added 73 receiving yards on 10 receptions to his total proving he is fully back in the offensive mix.
A human pinball 👏
📺: FOX
NFL+ // https://t.co/KTh0i4oaLh pic.twitter.com/RP1UjagL7Z— San Francisco 49ers (@49ers) September 7, 2025
This week, he and his Niners face a Saints defense that surrendered 108 yards to the running back position last week against the Cardinals. New Orleans allowed a combined 5.4 yards per carry in that game. Without Kittle, Aiyuk, and Jennings on the field, expect Mac Jones to lean heavily on his versatile running back giving McCaffrey plenty of opportunity to cash this prop.
Juwan Johnson Over 3.5 Receptions (-120 via Caesars)
Johnson emerged as one of his quarterback’s favorite targets last week against the Cardinals. The veteran tight end caught 8 of his 11 targets on the day. He wound up leading the team in both receptions and receiving yards. He ended last season with two six-reception games with Rattler under center in both of them.
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