NFL upset of the week: Giants will stun injury-ravaged 49ers
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Each week during the NFL season, we'll focus on one underdog with a chance to pull off the outright upset. Last week, we struck gold. Despite 14 favorites winning in Week 2 - tied for the most in NFL history - we nailed the Raiders (+210) as live underdogs against the Saints.

New Orleans is vulnerable again this week versus Green Bay, but another NFC contender is in even worse shape, as the depleted 49ers face a tricky test against the upset-minded Giants (+170) on Sunday.

Too many injuries for Niners

In a brutal Week 2 across the league, no team was hit harder than San Francisco. The Niners could enter Sunday's contest missing nine starters after a devastating string of injuries against the Jets last week at MetLife Stadium, where they'll play again versus the Giants.

Star defensive linemen Nick Bosa and Solomon Thomas are out for the season with torn ACLs. Quarterback Jimmy Garoppolo and running backs Raheem Mostert and Tevin Coleman also left Sunday's game and aren't expected to play this week, while tight end George Kittle and edge rusher Dee Ford are questionable.

Garoppolo's absence is reason enough to fade this team. Since Kyle Shanahan took over in 2017, the 49ers are 22-8 when Garoppolo attempts a pass and 4-19 when he doesn't, including 0-11 in road games. Nick Mullens - who'll likely be the starter Sunday - is 0-3 on the road during that span and has thrown more interceptions (11) than touchdowns (10) in his last nine starts.

Even those who do suit up Sunday could be tentative playing on the same field that resulted in so many injuries a week ago. Star lineman Trent Williams admitted that the turf will be on the team's mind, per Jennifer Lee Chan of NBC Sports Bay Area, which is concerning for a roster already thin on available talent.

Giants can exploit matchups

The 49ers survived the second half last week without Garoppolo and Co., but they can't expect to be so lucky against a Giants team that nearly erased a 17-point deficit this past Sunday in a narrow loss to the Bears.

New York's near-comeback came without star rusher Saquon Barkley, who is out for the year after tearing his ACL last week. Daniel Jones threw for 168 yards in the second half without his top offensive weapon and could be in for a big game against a Niners defense missing top corner Richard Sherman and much of its pass rush.

Conversely, the Giants' pass defense held Mitchell Trubisky below 200 passing yards and forced two interceptions. One of those was to James Bradberry, who blanketed top receiver Allen Robinson and should make life hard on Mullens and an already-depleted receiving corps.

Why the Giants will win

It's somewhat puzzling that the 49ers are still getting so much respect in this one. They were matched on the scoreboard in the second half of last week's win against the Jets without many of their key starters, and the Giants are easily a better squad than their crosstown rivals.

Shanahan has never won on the road without Garoppolo, and he'll struggle to do so with his C-team on Sunday. It may not be pretty, but trust the G-Men to take care of business at home.

(Odds source: theScore Bet)

C Jackson Cowart is a betting writer for theScore. He's an award-winning journalist with stops at The Charlotte Observer, The San Diego Union-Tribune, The Times Herald-Record, and BetChicago. He's also a proud graduate of UNC-Chapel Hill, and his love of sweet tea is rivaled only by that of a juicy prop bet. Find him on Twitter @CJacksonCowart.

NFL upset of the week: Giants will stun injury-ravaged 49ers
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