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NFL Week 11 ‘Monday Night Football’ game picks and predictions

Week 11 of the 2022 NFL season wraps up tonight with a lopsided NFC West clash. The San Francisco 49ers (5-4) travel to take on the injury-depleted Arizona Cardinals (4-6) on Monday Night Football. Read on for our picks and predictions.

Arizona Cardinals v San Francisco 49ers Photo by Ezra Shaw/Getty Images

Week 11 of the 2022 NFL season is almost over. It couldn’t quite live up to the spectacle of Week 10, with quite a few low-scoring games and a number of blowouts. Atlanta Falcons fans could rejoice, as the team defeated the Chicago Bears to snap a two-game losing streak. We also watched the Philadelphia Eagles narrowly avoid another upset, this time at the hands of the Indianapolis Colts, and the Dallas Cowboys absolutely dominating the Minnesota Vikings.

This week’s Monday Night Football matchup once again features a massive mismatch—at least according to the bettors. The San Francisco 49ers take on the Arizona Cardinals with Colt McCoy starting at QB and with a number of starters out of the lineup. This looks like a tough spot for Arizona, but division games can sometimes be closer than expected.

Let’s get right to tonight’s picks, which I’ll be making on a straight moneyline (aka picking the winner) basis. I’ll still provide the information on the spread and over/under, for those interested. At the bottom, I’ll show the rest of the staff’s picks for the game.

All odds are taken from DraftKings Sportsbook and are subject to change. See the current odds here.

Monday Night Football: San Francisco 49ers (5-4) at Arizona Cardinals (4-6)

The pick: 49ers -450

Spread: 49ers -10 | Over/Under: 43 | Moneyline: 49ers -450, Cardinals +360

I feel like the 49ers should be better than they are, but outside of beating up on the Rams twice and dominating the Panthers, San Francisco has just been sort of...good, not great. They’ll have an opportunity for a statement game against a division rival on Monday Night Football, as the Arizona Cardinals come to town with a number of crucial players injured. I expect the 49ers to take care of business, even though Colt McCoy is one of the better backup QBs in the league.

Staff picks

What are your picks and predictions for tonight’s Monday Night Football matchups?

Odds/lines subject to change. T&Cs apply. See for details.