2021 NFL picks, score predictions for Week 5

San Francisco 49ers (2-2) at Arizona Cardinals (4-0)

Sunday, October 10, 4:25PM ET

At this point, it’s really hard to pick against the Cardinals. They’ve been far from perfect this season, but they sport one of the most electric offenses we’ve seen in some time and keep finding ways to win on Sundays.

The same cannot be said for the San Francisco 49ers, a team that has now lost two straight games. Injuries continue to be problematic, and the offense isn’t producing enough to come away victorious. As great as many expected this team to be in 2021, it just hasn’t panned out — again, the caveat being that they’ve been ravaged by injuries.

With Trey Lance likely to be under center, the 49ers are not going to be up to the task of keeping pace with Kyler Murray and the Arizona offense. With two quality running backs, an MVP-candidate quarterback and four outstanding receivers, there’s just no way to contain them on the scoreboard.

The Cardinals get the best of the NFC West rivals, hanging 30+ points on a defense that was thought to be among the top groups coming into the season. Lance gets sacked at least four times, turns it over at least twice, and joins the rest of the rookie quarterbacks the season with an ugly start under his belt.

Prediction:  | Spread: Cardinals (-5.5)