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NFL Week 3 ‘Thursday Night Football’ game picks and predictions

After two straight weeks of very entertaining Thursday Night Football, Week 3 kicks off with one of the biggest spreads of the week as the New York Giants (1-1) travel to take on the San Francisco 49ers (2-0). Read on for our picks and predictions.

San Francisco 49ers v New York Giants Photo by Mike Stobe/Getty Images

We’ve had a pretty exciting opening two weeks here in the 2023 NFL season. After a week of defensive dominance, Week 2 featured a rebound by the offenses and a number of exciting comebacks. The New York Giants completed a 21-point comeback against the Arizona Cardinals, the Washington Commanders rallied from a big second-half deficit to defeat the Denver Broncos, and our Atlanta Falcons pulled off a 12-point fourth-quarter comeback against the Green Bay Packer.

Speaking of the Giants, this week’s Thursday Night Football game—while initially looking like a fairly spicy matchup between two NFC playoff teams from 2022—has quickly turned into an expected blowout. The San Francisco 49ers host New York, and given the Giants early struggles, this one could be a bloodbath.

Let’s get right to tonight’s pick, 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.

Thursday Night Football: New York Giants (1-1) at San Francisco 49ers (2-0)

The pick: 49ers (-575)

Spread: 49ers -10.5 | Over/Under: 43.5 | Moneyline: 49ers -575, Giants +425

In many weeks, this 10.5-point spread would be the largest in the NFL. That’s not the case in Week 3, but it’s still pretty close. That’s because the 49ers (2-0) have looked as dangerous as they were in 2022, dominating the Steelers in Week 1 and handling a dangerous-looking Rams team in Week 2. Coming to San Francisco for the home opener are the Giants (1-1), who should probably be 0-2 at this stage. While the Giants are a frisky team, they simply don’t match up well with the 49ers—and this one could get ugly quick.

Staff picks

What are your picks and predictions for tonight’s Thursday Night Football matchup?

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