
The San Francisco 49ers were among the more popular NFL betting picks for a title after their Super Bowl loss to the Kansas City Chiefs last season. The New York Giants, meanwhile, are getting some of the best NFL betting odds for the number 1 pick in next spring’s draft. While it could seem these teams are as far apart as could be, they’re also two of the teams most hard hit by injuries. In fact, the 49ers could be down as many as nine starters on Sunday — a brutal number for NFL Week 3 action. While the Giants aren’t quite that hard hit, they are now without their best player — Saquon Barkley — for the rest of the season after Barkley tore his ACL in Week 2 against the Bears.
As a result, neither team is anything like the teams online sports bettors expected at season’s start, and the injuries complicate NFL betting picks. For starters, no one knows if recently signed Devonte Freeman will be available for the Giants, and if so, how well he might be able to fill Barkley’s role. Without Barkley in the backfield, can second-year quarterback Daniel Jones continue to show progress, much of which has been predicated on the play-action threat? Secondly, given that the 49ers are returning to the field where they suffered most of their catastrophic injuries — MetLife Stadium, where they beat the Jets 31-13 in Week 2 but lost a number of players as well — might they withhold some players, as some pundits expect?
With such uncertainty, it’s hard to know what to make of NFL betting lines that currently hover around 49ers -4 and an over/under of 41 or 42.
Key matchups to watch

The biggest matchup of this NFL Week 3 tilt may prove to be the San Francisco 49ers against the injury report. When both teams are fully healthy, the talent on the 49ers squad—which came within a quarter of winning the Super Bowl last season—is vastly superior to that of the New York Giants. While there’s lots of history between these two teams, who have met eight times in the playoffs (and have split them evenly; the all-time series, meanwhile, is currently 21-20 in the Giants favor), they are at very different points as franchises right now. As a result, the Giants may face a 49ers squad that is much closer in terms of talent level, especially if coach Kyle Shanahan keeps additional players out as a result of injury concerns after numerous 49er players blamed the most recent spate of injuries on the “sticky” MetLife field.
Other potential key matchups include Devonte Freeman (assuming he plays for the Giants) against the depleted 49ers front seven and 49ers quarterback Nick Mullens (assuming he plays in Jimmy Garappolo’s place) against the weak Giants secondary. As well as the coaching matchup between two of the younger head coaches in the league, first-year coach Joe Judge of the Giants and the 49ers fourth-year head coach Kyle Shanahan.
New York Giants

For the New York Giants to break through against the San Francisco 49ers and earn their first win of the young season, the offensive line will need to step up against the 49ers’ depleted front seven. Standouts Nick Bosa, Dee Ford, and Solomon Thomas may be missing, but the 49ers have depth. Even beyond dominating the line, Devonte Freeman will need to perform. Freeman, who averaged a career-low 3.6 yards per carry last season, may or may not be up to the challenge, especially with only a few days to learn the Giants playbook.
Similarly, even with the 49ers decimated by injuries, coach Joe Judge will need to out-scheme Kyle Shanahan, long regarded as one of the best offensive minds in the league. Judge will have to have his defense prepared for either Jimmy Garappolo (whom he knows from when both were with the Patriots) or backup Nick Mullens (who seems more likely to make the start as Garappolo recovers from the high ankle sprain suffered in Week 2 against the Jets). So far this season, Judge hasn’t shown that capacity. Not that many coaches can match up against Shanahan, but Judge has looked like a rookie head coach in both the Week 1 26-16 loss to the Steelers and the Week 2 17-13 loss to the Bears, with several head-scratching calls in each game.
Finally, regardless of who starts at quarterback for the 49ers, the Giants secondary will need to step up. Few coaches can scheme players into space the way that Shanahan can, and though the Giants have given up only 377 passing yards total in the two losses (second only to the Colts), that number is deceiving. The Steelers focused on the ground game in Week 1 and the Bears, at least with Mitchell Trubinsky at quarterback, hardly represent NFL-quality passing. As a result, the Giants secondary—which was regularly torched last season, ranking 27th in expected points contributed by pass defense.
San Francisco 49ers

For the San Francisco 49ers to leave MetLife Stadium with a second consecutive win in NFL Week 3, their depleted roster will simply need to outperform the New York Giants in at least a few key areas.
Even with a depleted roster, the 49ers hold numerous advantages. First, they quite simply are a deeper team, even with as many injured players. Even most Giants fans will admit Dave Gettleman hasn’t drafted very well for the Giants; 49ers general manager John Lynch, meanwhile, is regularly considered one of the best evaluators of talent in the league. Secondly, the 49ers have a significant advantage at head coach, where Shanahan adapts to his personnel as well as anyone else in the league.
As a result, expect to see the 49ers take advantage of Mullens’ quick release and use lots of scheming to create plays in space. Even if the Niners are down their top two backs in Raheem Mostert and Tevin Coleman, expect to see Jerick McKinnon and Jeff Wilson Jr., as well as possibly JaMycal Hasty, who was named as their protected practice squad player Wednesday, meaning it’s likely he’ll see game action. Ex-Giants back Paul Perkins also got a look and is a candidate for a free agent signing.
NFL Week 3 Preview Summary
Thus far, this hasn’t been the season either the San Francisco 49ers or New York Giants has expected. How they respond in NFL Week 3 action, however, will set the tenor for the rest of the season. Should the Giants fall to 0-3, they can start preparing for a high draft pick—and Gettleman’s seat as GM may start getting a bit warmer. If the 49ers fall to 1-2, the NFL betting odds of their return to the Super Bowl will likely change drastically.
The focus for the Giants should be the future, especially with one of their cornerstone players now out for the season, but that doesn’t mean they shouldn’t look for a win against a battered 49ers squad. The 49ers, meanwhile, will look for players hungry to prove themselves; in this case, Shanahan’s track record would seemingly still make them a safer pick, though the uncertainty is reflected in the otherwise relatively tight NFL betting lines seen at many a sportsbook casino right now.

Betting Picks and Predictions
Some online sports betting will likely avoid the uncertainty of this game, but with NFL betting lines currently looking like San Francisco 49ers at -4 and an over/under of 41 or 42, there’s certainly still some intrigue. A few trends to watch: The 49ers are currently 2-0 against the spread, and the New York Giants’ underwhelming offense has recommended the under in both of their losses.
Our prediction: San Francisco 49ers 24, New York Giants 10