Top 5 Players Who Will Determine Cardinals vs 49ers

The urgency won't be any higher for the Arizona Cardinals to get a win this season than their final showdown with the San Francisco 49ers. Arizona remains winless in NFC West division games at 0-3, and a loss guarantees them a losing division record with two games against the Los Angeles Rams still on deck.

Conversely, the 49ers can secure a winning record in the division with a win. It's a high-stakes game for both sides, but the Cardinals need this far more.

How the game will shake out will depend entirely on each team's top players. The Cardinals are the healthier team than the 49ers entering this game, but that speaks far more to how banged up San Francisco is.

The Niners are missing Nick Bosa, Fred Warner, Brandon Aiyuk, and seemingly countless others. The Cardinals will suit up without Marvin Harrison Jr. and Will Johnson.

It sets this game up to be gritty and emotional, but both teams still have plenty of good players and Pro Bowl talents.

We're looking once again at the five best players in this game for either team with a side note on the quarterbacks. I try to make sure to not just highlight the same players every week, but it's starting to become impossible for one Arizona Cardinal in particular...

That said, let's look at Jacoby Brissett and the return of Brock Purdy.

The quarterbacks...

Brissett has nearly 200 more passing yards in one fewer start than Kyler Murray since he took over. He also has more passing touchdowns (8) and fewer interceptions (1). Although Brissett hasn't brought the same rushing potential that Murray does for the offense, he's dramatically increased the offense's potency. There's no doubt that Brissett is the best option for the Cardinals down the stretch.

The 49ers will welcome back Purdy, who has been missing since Week Two due to injury. Mac Jones played well in relief for him, and he could still be called upon if Purdy proves he's not ready yet. However, Purdy is the starter until we're told otherwise. In two games, he has four touchdown passes and four interceptions. We really have no clue what to expect, but that's not something encouraging for 49ers fans. Thankfully, Kyle Shanahan is still calling games.

5. George Kittle

Kittle is just one of the many 49ers who have been dealing with injuries this season, but he remains one of the best tight ends in the league when he's on the field. He's caught all 13 of his passes for 116 yards and a score in his last two games after returning from injury.

With Purdy back in the fold, it will be difficult to guess how this offense will work, but we know that Kittle will be involved early and often to get him settled in after missing nearly two months.

4. Josh Sweat

Sweat has legitimately been one of the best pass rushers in the league this year. The former Eagle has eight sacks and three forced fumbles on the season along with 10 tackles for loss.

He's proven to be worth every penny and is carrying a pass rush that is struggling to do much outside of him and Calais Campbell. The 49ers' offensive line isn't the worst, but it's a unit that Sweat can beat up and keep adding sacks to his impressive 2025 resume.

3. Trent Williams

"Silverback" is an ageless wonder. The future Hall of Famer is in his 16th season, and I truly don't know if you can name five offensive linemen, not just tackles, playing better than him at the ripe age of 37. Williams anchors this front five, and they will go as far as he does.

He's allowed three sacks this season, so he isn't as elite as years past, but he's run blocking as well as he ever has. The Cardinals will need to dial up packages to get after the quarterback, but Williams by himself will make that much more difficult.

2. Trey McBride

I promise that I try to rotate the top players each week, but I'm not sure I can justify leaving McBride out again this season; he's simply playing at another level.

McBride is having a historic season at the tight end position, as he's on pace to finish just shy of the single-season tight end receptions record with 115 to go with more than 1,100 yards and 11 scores. He's improved in each year since entering the pros, and it feels like he still hasn't reached his full potential.

With Fred Warner out for the year for the 49ers' defense, McBride should eat them alive and post massive numbers.

1. Christian McCaffrey

When healthy, and that's something that's never guaranteed on a week-to-week basis, McCaffrey is one of the league's best offensive players.

His rushing stats have been underwhelming, with well under 4.0 YPC, but he's still on pace for 1,000 rushing yards. He can set more receiving yard records for the running back spot with his current pace for nearly 1,200 yards and 117 catches.

Almost no one has had a solution for CMC this season, and the Cardinals will have their hands full with a likely heavy workload on the table.