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49ers vs. Cardinals: NFL Week 16 Picks and Game Predictions

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49ers vs. Arizona 1

The Arizona Cardinals (8-6) are trying to hold onto the final wild card in the NFC as they host the San Francisco 49ers (5-9) on Saturday afternoon. The 49ers’ conference title defense got off to a rocky start in Week 1 after blowing a late lead to the Cardinals, and now Kyle Shanahan’s team is eliminated from the playoffs and will finish last in the NFC West.

San Francisco 49ers vs. Arizona Cardinals

Saturday, December 26, 2020 – 04:30 PM EST at State Farm Stadium

The Cardinals are a 4.5-point favorite at most NFL betting sites. Quarterback Kyler Murray is coming off his first 400-yard passing game in a 33-26 win over the Eagles. San Francisco lost 41-33 in Dallas after tying a season-high with four turnovers, including three by backup quarterback Nick Mullens. He has 16 turnovers this season and is questionable with an elbow injury.

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San Francisco: Down to Pride

For the 49ers, these last two games are really just about pride and finishing out a tough season that has been ravaged by injuries and the pandemic. The team would be wise to shut down tight end George Kittle for the season and not bother bringing him back with the playoffs officially out of reach. This offense is already down Jimmy Garoppolo and Deebo Samuel, so the main pieces have not been able to stay on the field together this season.

One of the bright spots for the offense has been the play of first-round rookie wide receiver Brandon Aiyuk. He has 568 receiving yards in just the last six games of his season, breaking over 70 yards in every game. He could make this a great receiving corps next year with a healthy Kittle and Samuel.

Defensive coordinator Robert Saleh will likely be one of the top candidates for the next round of head coach hires. His unit has been up and down this season, but it was always going to be hard with the early injuries to Nick Bosa, Richard Sherman, and others. He will have his hands full with this Arizona offense again. The Cardinals are one of four offenses this year to have over 400 yards against the 49ers. Murray has led Arizona to 24-to-26 points in all three of his starts against the 49ers.

Arizona: The Kyler Murray and DeAndre Hopkins Show

For Arizona to return to the playoffs, it will be on Kyler Murray and DeAndre Hopkins to continue carrying the load in these two crucial division games coming up. Hopkins has 1,324 yards this year while no other Arizona receiver is over 550 yards. Larry Fitzgerald caught only his first touchdown of 2020, albeit a great one, on Sunday as he is a role player at best at 37 years old. Hopkins had a season-high 169 receiving yards on Sunday, beating out his previous season high of 151 yards against these 49ers. Shame on the 49ers this time if they do not adjust better seeing as how Hopkins is by far the preferred weapon in Arizona this season.

Kenyan Drake and Chase Edmonds sometimes provide a solid ground attack, but Murray is truly the team’s most effective rusher with 741 yards and 11 touchdowns. He rushed for 91 yards against the 49ers in Week 1.

Arizona has been able to win shootouts at home this year over the Seahawks, Bills, and the Eagles on Sunday. The defense has only been able to hold three NFC East teams and the Jets to under 20 points this season. However, a healthy San Francisco offense was held to 20 points in the Week 1 meeting. This has been a difficult year with lead pass-rusher Chandler Jones going down after five games, but Haason Reddick has stepped up with a career season, including five sacks against the Giants in Week 14.

DeAndre Hopkins #10 of the Arizona Cardinals. Norm Hall/Getty Images/AFP


This is an interesting spread for this weekend’s NFL picks because the 49ers play very few close games this season. In fact, they are tied for a league-low five games that had a fourth-quarter comeback opportunity with a team down one score and in possession of the ball. The 49ers are 1-4 in such games. Of San Francisco’s nine losses, the only one by fewer than five points was Arizona’s 24-20 comeback win in Week 1.

Kyle Shanahan’s offensive scheme is still effective enough to produce points if Mullens can avoid the turnovers, and the familiarity with Arizona should help. However, I think the Cardinals are in a good spot offensively again and have played this San Francisco team well all three times under Kliff Kingsbury and Murray so far. The Cardinals are just the better team at this moment in time.

With the playoffs out of reach for one team, I think the Cardinals take control of this game early and hang on to cover the spread to get to nine wins.

NFL Pick: (visit our Sportsbook Review)