The 49ers have seen their favored status grow with the return of Brock Purdy and Ricky Pearsall, but no reinforcements are coming for a defense that has struggled since losing multiple stars. Even With Marvin Harrison Jr. sidelined, I expect Brissett to have success in the passing as he has since taking over the starting role with four straight games over 250 pass yards while facing Seattle, Green Bay and Indy. This shouldn't be as tough a matchup as any of those games, and the bump for the 49ers offense means he's more likely to be in a chase scenario and stacking up yards as well. I'd consider a 250+ alt as well.

There may be a bit of rust on Brock Purdy and Ricky Pearsall coming back, but there's no doubt the 49ers offense levels up with them on the field. While the Cardinals do appear to operate better with Jacoby Brissett behind center, they are missing Marvin Harrison Jr. on Sunday, and they've lost to every quality defense they've faced this season. San Francisco knows this is crunch time – it must start not only winning but playing playoff-level football to salvage this season. Just because Arizona has played mostly close games does not mean that will continue.

Brock Purdy is back in the lineup for the 49ers, who managed to hold their own while Mac Jones was taking snaps in Purdy's absence. Slowly, SF has been getting back some pieces, with George Kittle returning to active duty a few weeks ago, with the best news that Christian McCaffrey has stayed off of the injured list and should resume his Batman & Robin role with Purdy. We are also wondering about the Arizona side, which regressed last week at Seattle after an uplifting win over the Cowboys, and if Jacoby Brissett really is more than a stop-gap answer at QB as the Big Red seem to be putting all of their eggs in his basket for the rest of this season. Play 49ers

Cardinals safety Jalen Thompson made just 14 combined tackles in his last three games, but this is a terrific matchup with the 49ers. San Fran is the only team that has generated 160 tackles for opposing defensive backs. The Cards are dealing with key injuries in their secondary. Thompson recorded six tackles against San Fran earlier this season, and I think he has a good chance to hit seven Sunday.

DraftKings. Tatum Bethune has recorded at least ten tackles in five straight games. Wearing the blue dot in the absence of 49ers All-Pro Fred Warner, Bethune has been everywhere defensively for the 49ers. The Cardinals offensively have been more efficient with Jacoby Brissett taking the snaps - and they’ll be without big play threat Marvin Harrison on Sunday. I’m expecting more check-downs in the passing game, which should benefit Bethune’s tackle opportunities.

The 49ers are not only getting Ricky Pearsall back in the lineup but also Brock Purdy ahead of their divisional clash with Arizona. Prior to Pearsall suffering an injury he was functioning as the teams WR1 and was Purdys primary target Weeks 1-4. He will face a subpar Cardinals pass defense that will be without their best cornerback in rookie Will Johnson, leaving potentially a huge mismatch for Pearsall with backup CBs Denzel Burke and Max Melton. We’re getting a sizable discount on this line.

Brock Purdy will be back, Ricky Pearsall probably will be for the Niners and Marvin Harrison Jr. is out for Arizona. I'm actually not sure 2025 Brock Purdy is better than 2025 Mac Jones and that's probably why this spread hasn't really moved with the Purdy news. Just seems like Arizona has quit -- if you read Wednesday's premium newsletter for subscribers, I went into some detail (and odds futures) on the Cards. Me playing a road ML team in the NFL ... checking my pulse. No stroke yet. Just feels like the season for the Niners.

San Fran's injury-plagued defense, which was torched last Sunday by the Rams, gets a reprieve of sorts with a major injury development for 'Zona. Marvin Harrison Jr., the Cardinals' top WR (and No. 2 on the team in receptions) is out after an appendicitis. The Cards previously lost WR Zay Jones for the season, so backup QB Jacoby Brissett must rely on lesser lights. The Niners, showing resilience, bounced back this season from their three previous defeats with SU wins. Most sportsbooks were posting a line of three on Wednesday, and the lower half-point could make a difference.

Both of these teams are dealing with key defensive injuries, but I'm willing to back the Cardinals because I believe they should be favored if they aren't missing too many guys. That's because the Arizona offense has been good with Jacoby Brissett at QB, scoring 22+ in all four of his starts despite facing the Colts, Packers and Seahawks in that stretch. The 49ers defense has given up 23+ in six of the last seven games and couldn't stop a beat-up Houston offense a few weeks ago. Last week was the first time all year the Cardinals lost by more than four points, and the 49ers haven't been playing well enough to be considered among their toughest opponents, especially with the game in Arizona.