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It’s hard to believe now, but back when the 49ers and Cardinals first squared off in September, the winner was guaranteed to take over sole possession of first place in the NFC West.

Both teams were 2-0, the Seahawks had lost to the 49ers in Week 1, and moments before kickoff on Sunday, Sept. 21 at Levi’s Stadium, the Eagles dealt the Rams their first loss of the season in Philadelphia.

The 49ers’ 16-15 win moved them in front of their competition inside the division, but a wave of injuries has set the team back. Now, Kyle Shanahan’s 6-4 squad is looking for a second win over a Cardinals team that has lost several top players in recent weeks.

What’s in store for the return of Brock Purdy, Ricky Pearsall, and a rejuvenated 49ers’ offense against Arizona? Here are our predictions.

Kawakami: Brock Purdy. I don’t love picking a player who has missed eight of the last nine games and remains questionable for Sunday, but Purdy’s had some of the biggest performances of his career against the Cardinals. It’d make sense if this game had been circled for a while as a return target. And the 49ers could use the emotional boost.

Lombardi: Purdy. I have to double dip on this one. Beyond all the reasons Tim listed, Purdy will be back in his home region. And his fellow Arizonan, Pearsall, will be making a concurrent return to the lineup. The two have accounted for the majority of the 49ers’ explosive passing production in the limited time they’ve been simultaneously healthy.

Kawakami: Bryce Huff. Even in their pass rush’s reduced state, there will be sacks on the table for the 49ers against Jacoby Brissett, who is a solid passer but not exactly elusive in the pocket. I’ll write Huff down for 1.5 sacks, maybe including a forced fumble.

Lombardi: Keion White. His sack against the Los Angeles Rams was impressive. It involved a win against the right tackle and a recovery from a prone position after the right guard had scurried over to help and knocked White down. White never gave up, rising to his feet to corral Matthew Stafford. He’ll get Jacoby Brissett on Sunday — maybe more than once.

Kawakami: Shanahan in November and December. When the 49ers have made the playoffs in the Shanahan era, they’ve usually turned it up from November on, including a six-game winning streak in late 2023, a 10-game streak in 2022, (starting on Oct. 30), and a 7-2 finish in 2021.

Lombardi: The easy part of their schedule. The defense is leaking oil, but the challenges over the next month won’t be nearly as stiff. Arizona’s offense ranks No. 21 by expected points added (EPA) per play. Then, the 49ers play the No.26 Carolina Panthers, the No. 30 Cleveland Browns, and the No. 32 Tennessee Titans. This stretch is tailor-made for a team looking to salvage a young and depleted defense.

Kawakami: 49ers takeaways. The 49ers are 4-1 this season when they’ve forced at least one turnover. Unbelievably, they’ve gone without a takeaway in five other games — half the season, including the last two weeks. I don’t think the 49ers necessarily need a turnover to win this game, but if they get one (or two or three), it’d make things a lot easier.

Lombardi: Time of possession. Hog the ball. That’s the 49ers’ formula to shield their defense and they should now, with Purdy and Pearsall both back, be better equipped than at any other point of 2025 to execute it.

Kawakami: 49ers 27, Cardinals 21. If Purdy plays, he’ll probably be a little rusty, so it might be a stretch to predict the 49ers’ second trip beyond 26 points this season. But he’ll move the ball. And I’ll keep riding the pattern — the 49ers have alternated wins and losses in the previous eight weeks and need a victory in Arizona to make it nine.

Lombardi: 49ers 31, Cardinals 20. This week, Arizona grew more injured than the gradually healing 49ers, who will now (remarkably) face a team that’s more beaten up than them. The drop-off in schedule difficulty seems to pair very well with the 49ers’ key returns on offense. It’s a perfect time for Shanahan’s team to make a statement.