A week after defeating the Jets at the Meadowlands, the San Francisco 49ers return to MetLife Stadium to face the New York Giants. The Giants are dealing with the loss of running back Saquon Barkley for the season while San Francisco has a bevy of injuries of their own from last week. Still, New York’s offense will have issues with the 49ers defense and San Francisco’s offense has enough weapons to leave New York with a second victory. San Francisco 49ers vs. New York Giants Betting Odds San Francisco’s biggest question mark in this game is the quarterback after Jimmy Garoppolo left last week’s game with a high ankle sprain. He has not been ruled out of Sunday’s game with the Giants, but I would be surprised if he goes back out there, so the 49ers will turn to Nick Mullens. He’ll have fewer running backs at his disposal with Tevin Coleman and Raheem Mostert both ruled out of the game, but tight end George Kittle should return for the Niners. San Francisco might simplify its offense with all the injuries and that could work against a Giants defense that has been surprisingly strong so far this season. The Giants offense isn’t dependent upon Barkley, but his presence was certainly a major key in the team’s success. Without Barkley for the rest of the season, the Giants’ rushing attack is far less dangerous and that will allow teams to put pressure on Daniel Jones. It’s been a rough start to the season for Jones against two good defenses as he’s already been dropped seven times and he’s thrown three interceptions. San Francisco’s pass rush isn’t as ferocious without Nick Bosa and Solomon Thomas, but that secondary should still feast on Jones and make him pay for his mistakes. A full game with Mullens at quarterback could mean this will be a low-scoring affair. Mullens completed eight of his 11 passes after coming in for Garoppolo last week, but he was sacked twice and threw an interception. Jones will struggle with the 49ers defense, so I don’t expect many points to be scored between these two teams. I’m again going to look at the alternate totals for this game and say there will be fewer than 36.5 total points scored in the game, which is offered at +160 odds. San Francisco 49ers to win I understand that the 49ers were hit by injuries on their defense, but it’s an insult to make them only 4.5-point favorites over the Giants. The New York offense has been a mess and the 49ers still have a good running game and George Kittle to help whoever starts at quarterback for San Francisco. I won’t push the envelope too much with this NFL betting prediction, but I’m going to take San Francisco laying 7.5 points at +150 odds on the New Jersey online sports betting site.