This article is part of our NFL Picks series.
Arizona Cardinals 
@ San Francisco 49ers 
Betting Preview and Expert Picks for Week 18
Ohio launched sports betting to kick off the new year and those located in the Buckeye State can get in on the action at BetMGM with the BetMGM Ohio Bonus Code for up to $1,000 in first bet insurance.
The Cardinals (4-12) make the short trip to face the San Francisco 49ers (12-4) for an NFC West regular-season finale at Levi's Stadium.
The Cardinals, long eliminated from postseason contention, will afford David Blough a second consecutive start after he just narrowly missed leading Arizona to a win against the Atlanta Falcons in Week 17. Meanwhile, the 49ers will roll out their usual starters and also get back both Elijah Mitchell (knee) and Deebo Samuel (knee/ankle) from multi-game absences as they try to do their part to secure the No. 2 seed in the NFC, at minimum.
Arizona Cardinals at San Francisco 49ers for Week 18
*Best lines at time of writing listed
Moneyline: Cardinals +750 (DraftKings Sportsbook)/ 49ers -800 (PointsBet Sportsbook)
Point spread: Cardinals +14.5 (PointsBet Sportsbook)/ 49ers -14 (BetMGM Sportsbook)
Total: Over 39.5 points (DraftKings Sportsbook)/ Under 39.5 points (DraftKings Sportsbook)
The spread has unsurprisingly only grown in San Francisco's favor since it opened at 10.5 in the middle of last week. Following Week 17 results, which included another Eagles loss that kept the Niners in play for the No. 1 seed in the NFC, the number quickly shot up to 13 and has continued to be bet up to as high as 14.5 at some sportsbooks.
In comparison, the total has been much more stable. It was never going to be very elevated considering the extremely low expectations for a Cardinals offense missing Kyler Murray (IR-knee), James Conner (shin) and DeAndre Hopkins (knee) against the 49ers on the road, so the fact it's shrunk from an already tiny 40 points to 39.5 at multiple sportsbooks isn't surprising.
Sign up at PointsBet if you're in Ohio with the PointsBet Ohio promo code for up to $500 in second chance bets.
Arizona Cardinals at San Francisco 49ers Betting Picks This Week
If there were ever a game whose prognostication essentially wrote itself, this one would be a formidable candidate. As the mammoth point spread clearly indicates, this sets up as a significant mismatch in both incentive and talent, which sets up very well for the home team.
The 49ers' aforementioned postseason-related motivation and the returns of Mitchell and Samuel give rookie quarterback Brock Purdy, who's already far exceeded expectations after being thrust into the starting role in Week 13, his healthiest array of weapons yet.
In turn, the Cardinals' list of absences on offense already put them behind the proverbial 8-ball against a defense that's allowing the second-fewest yards per game (303.4). To make matters worse, the outlook on the other side of the ball isn't much brighter – starting cornerbacks Antonio Hamilton (hip) and Marco Wilson (neck) will miss the game for the Arizona.
Blough played serviceably against Atlanta's mediocre defense a week ago, but even the full week of practice during Week 18 prep isn't likely to help given he'll be down his top running back and wide receiver against a defense of a much higher caliber.
Consequently, this is the type of game to swing for a bet involving the heavy favorite that affords you plus money and banks on the Cards struggling to do much of anything on offense.
Cardinals at 49ers Best Bet: 49ers moneyline and Under 39.5 points (+115 at FanDuel Sportsbook)
Arizona Cardinals at San Francisco 49ers Prediction
49ers 27, Cardinals 6
As discussed, this sets up as a spot where there isn't any reason for the Niners not to win going away. While the temptation to take Arizona lightly will certainly be there, it's doubtful San Fran succumbs to it considering what it has at stake and the fact the offense is returning to full health. I'm tempted to even give the Niners a 30-spot – something they're certainly capable of – but I think they take their foot off the gas in the 4th quarter.
