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49ers vs. Cardinals Prediction: Will Arizona Cover in Season Finale?

49ers vs. Cardinals 49ers vs. Cardinals

NFC West rivals will meet in a game with zero playoff implications when the Cardinals host the 49ers at 4:25 p.m. ET. With Arizona laying 5 points as a home favorite and the total sitting at 42.5, what’s the best bet in today’s 49ers vs. Cardinals matchup?

Game Matchup & Betting Odds

San Francisco 49ers (+5) at Arizona Cardinals (-5); o/u 42.5

State Farm Stadium, Glendale, AZ

4:25 p.m. ET, Sunday, January 5, 2025

49ers vs. Cardinals Public Betting: Bettors Leaning with SF

Our NFL Public Betting Information page indicates that 57% of public bettors are currently backing the 49ers when it comes to the spread. This information is subject to change throughout the day, however, so be sure to check the link so you’re receiving the most up-to-date public betting data.

Guerendo removed from injury report

Isaac Guerendo (foot/hamstring) was removed from the injury report and will play in Week 8 against the Cardinals. This is perhaps the healthiest Guerendo has been in weeks. He practiced in full all three days and is ready to shoulder the load against the Cardinals. The big-bodied, speedy rookie has decent odds of surpassing the 13 touches he racked up last week. He played particularly well in the passing game, catching 4-of-4 targets for 65 yards. With the 49ers potentially shaking up the offensive personnel this offseason, it would be unsurprising to see Kyle Shanahan further audition Guerendo for passing-down contributions.

Conner will not play Week 18

James Conner (knee) will not play in Week 18 against the 49ers. The Cardinals placed Conner on injured reserve shortly after ruling him out on Wednesday. Michael Carter was signed to the active roster in a corresponding move. Conner entered Week 17 with a knee issue and didn’t make it far before being shut down. He re-aggravated the injury after four carries and did not return. His season comes to a close with 236 carries for 1,094 yards and eight touchdowns.

While it was another strong season for the veteran, he went from averaging 80 rushing yards per game in 2023 to 68 this year. On the other hand, Conner more than made up for the slight downturn in rushing production with 47 receptions for 414 yards and a touchdown through the air, dwarfing his 2023 receiving numbers. Late-season injury aside, Conner showed no signs of slowing in his age-29 season and even earned a two-year contract extension mid-season. He could cede more work to Trey Benson next year, but Conner is still firmly in the RB2 mix heading into 2025.

The total has gone OVER in 5 of San Francisco’s last 6 games when playing Arizona

San Francisco is 4-1 SU in its last 5 games when playing on the road against Arizona

The total has gone OVER in 5 of Arizona’s last 6 games when playing San Francisco

Arizona is 4-1 ATS in its last 5 games at home

49ers vs. Cardinals Prediction:

Take Arizona. The 49ers are too banged up to back today in Arizona. Quarterback Brock Purdy is out with an elbow injury and Deebo Samuel will be held out due to rib and wrist injuries. Tight end George Kittle is questionable with ankle and hamstring injuries and a slew of other players are either doubtful or questionable on both sides of the ball. Today will be the end of a lost season for a 49ers team that played in the Super Bowl a year ago.

49ers vs. Cardinals NFL Prediction: ARIZONA CARDINALS -5