NEW ORLEANS (Sept. 14, 2025) — The New Orleans Saints will look to rebound from their season-opening loss when they welcome the San Francisco 49ers to the Caesars Superdome on Sunday. Kickoff is set for 12:00 p.m. CDT, with regional coverage on FOX (WVUE-8 locally).

Sunday’s contest will mark the 79th regular season meeting between the two storied franchises. San Francisco holds a 49-27-2 advantage in the all-time series, though New Orleans has managed to win six of the last 10 matchups, making the rivalry one of the league’s most competitive in recent years.

Saints Searching for First Win

The Saints (0-1) enter Week 2 eager to erase the sting of their 20-13 loss to the Arizona Cardinals in their season opener. Despite a late rally engineered by second-year quarterback Spencer Rattler, New Orleans came up just short, falling victim to missed opportunities and costly penalties.

Rattler threw for 214 yards without an interception and showed flashes of poise in crunch time, but the offense struggled to finish drives. Running back Alvin Kamara provided the team’s lone touchdown with an 18-yard score, and the Saints were flagged 13 times for 89 yards — a trend rookie head coach Kellen Moore knows must be corrected if his team hopes to upset a Super Bowl contender this week.

“We’ve got to clean up the details,” Moore said postgame. “Penalties and mental mistakes put us behind the chains, and against good teams, that’s tough to overcome.”

49ers Riding High

San Francisco (1-0) travels to New Orleans after a strong start to the season. The 49ers opened their 2025 campaign with a decisive performance, showcasing balance on both sides of the ball. Led by quarterback Brock Purdy and a deep arsenal of offensive weapons, San Francisco once again looked like a team capable of making another deep postseason run.

The 49ers have long thrived on physicality and versatility. With running back Christian McCaffrey healthy and wideouts Deebo Samuel and Brandon Aiyuk stretching defenses, Purdy has no shortage of options. The 49ers defense, anchored by All-Pro pass rusher Nick Bosa, remains among the most feared units in the league, and will be licking its chops against a Saints offense still finding its rhythm.

Key Matchups to Watch

• Saints Offensive Line vs. Nick Bosa & 49ers Pass Rush: Protecting Rattler will be paramount. Arizona pressured the young quarterback heavily in Week 1, and San Francisco brings an even more imposing front.

• Alvin Kamara vs. 49ers Linebackers: Kamara remains the focal point of New Orleans’ offense, both on the ground and through the air. His ability to slip tackles and extend plays will be tested against one of the league’s fastest linebacker groups.

• Saints Secondary vs. Deebo Samuel/Brandon Aiyuk: The New Orleans defensive backfield will have its hands full trying to contain San Francisco’s dynamic duo, particularly with McCaffrey demanding attention out of the backfield.

Series History

This will be the 79th regular season meeting between the teams, with the rivalry tracing back to the Saints’ early days in the NFC West. While San Francisco dominated much of the series in the 1980s and 1990s, the Saints have held their own in recent years. Memorable matchups include New Orleans’ thrilling 25-22 victory in 2021 and San Francisco’s 2019 defensive shutout.

NFC South Outlook

The rest of the division also faces tough road tests this week:

• Carolina Panthers (0-1) visit the Arizona Cardinals (1-0) on Sunday afternoon.

• Atlanta Falcons (0-1) travel to face the Minnesota Vikings (1-0) on Sunday Night Football.

• Tampa Bay Buccaneers (1-0) take on the Houston Texans (0-1) on Monday Night Football.

For New Orleans, an early-season victory over San Francisco would not only put them back at .500 but also serve as a statement win for Moore in just his second game as head coach.

Outlook

The 49ers arrive as favorites, but the Superdome has often provided the Saints with one of the strongest home-field advantages in the NFL. For Rattler, this matchup represents another chance to prove he can lead the Saints in high-pressure situations, while Moore seeks his first career victory on the sideline.

Prediction: 49ers 27, Saints 17