NFL Week 1: 3 teams on upset alert this Sunday

2. The San Francisco 49ers could have some trouble with Arizona

The reigning NFC champions are favored to make another run at the playoffs but this first matchup could be tricky. A date with the upstart Cardinals, who had a very good offseason, could provide quite a challenge for San Francisco.

Arizona may still be a year away from contending for the division title, but second-year quarterback Kyler Murray should keep them competitive more often than they were a year ago. Murray will also benefit from the arrival of DeAndre Hopkins, giving him a true number one receiver to test the 49ers’ secondary.

San Francisco also had its fair share of difficulty with the Cardinals last season, winning the two matchups by a combined 13 points. There are also questions about how the 49ers’ defensive line will look without DeForest Buckner, who was traded in the offseason, and injury questions on offense as Deebo Samuel may be on a pitch count in this game as he comes off a broken foot.

Home field would usually be a difference-maker here but the 49ers are among the many teams who won’t have fans in the building this weekend, creating a true neutral site feel for this game. Don’t be shocked if Arizona gives San Francisco a huge run for its money here.