49ers vs. Cardinals Prediction, Odds, Spread, Injuries, Trends for NFL Week 11

Iain MacMillan | Nov 11, 2025

The Cardinals are home underdogs against the 49ers in NFL Week 11 action. / Kyle Terada-Imagn Images

The San Francisco 49ers are now on the outside of the NFC playoffs looking in after falling to 6-4. That makes their Week 11 game against the Arizona Cardinals a big one as they try to leapfrog the Chicago Bears and get back into a wild-card berth.

The Cardinals' season is likely over at 3-6, but that doesn't mean they won't go down swinging. Let's dive into the odds and my best bet for this weekend's NFC West showdown.

49ers vs. Cardinals Odds, Spread, and Total

Odds via Caesars Sportsbook

Spread

• 49ers -2.5 (-121)
• Cardinals +2.5 (+102)

Moneyline

• 49ers -150
• Cardinals +124

Total

• OVER 48.5 (-102)
• UNDER 48.5 (-113)

49ers vs. Cardinals How to Watch

• Date: Sunday, November 16
• Game Time: 4:05 pm ET
• Venue: State Farm Stadium
• How to Watch (TV): FOX
• 49ers Record: 6-4
• Cardinals Record: 3-6

49ers vs. Cardinals Betting Trends

• 49ers are 6-13 ATS in their last 19 games
• The OVER is 5-2 in the 49ers' last seven games
• The OVER is 6-2 in the 49ers' last eight road games
• 49ers are 3-8 ATS in their last 11 games vs. NFC West opponents
• Cardinals are 13-7 ATS in their last 20 games
• The OVER is 6-1 in the Cardinals' last seven home games
• Cardinals are 9-2 ATS in their last 11 games when set as underdogs

49ers vs. Cardinals Injury Reports

49ers Injury Report

• Alfred Collins, DT - Questionable
• Brandon Aiyuk, WR - PUP-R
• Rickey Pearsall, WR - Questionable
• Brock Purdy, QB - Questionable
• Mykel Williams, DE - IR

Cardinals Injury Report

• Mack Wilson Sr., LB - Questionable
• Xavier Weaver, WR - Questionable
• Max Melton, CB - Questionable
• Will Johnson, CB - Questionable
• Simi Fehoko, WR - Out

49ers vs. Cardinals Key Player to Watch

• Marvin Harrison Jr., - Arizona Cardinals

Marvin Harrison Jr., hasn't quite lived up to the expectations that were set out for him before the 2024 NFL Draft, but he is still good enough to be the Cardinals' top option at wide receiver. He has a favorable matchup against a 49ers secondary that has struggled of late. That could set Harrison Jr. up to have a big game on Sunday.

49ers vs. Cardinals Prediction and Pick

In this week's edition of the Road to 272 Bets, I broke down why I'm taking the points with the Cardinals as home underdogs:

I'm not very high on the San Francisco 49ers, who showed their true colors last week against the Rams. The metrics show the 49ers as the definition of an average team, ranking 15th in both net yards per play and DVOA. Defensively, they have fallen to 26th in opponent EPA per play and 30th in success rate. Only the Cowboys and Bengals defense ranks worse in success rate. They may be able to hit their stride when they get healthy later in the season, but things are quietly looking dire for the 49ers right now.

The Cardinals also haven't been much to write home about this season, but they're getting a field goal's worth of points against a 49ers team that is falling apart, and it seems. I'll take the field goal in this NFC West battle.

Pick: Cardinals +2.5 (+102) via Caesars

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