Saturday, 4:30 p.m. ET | Amazon Prime
Matchup rating: 66.6 | Spread: ARI -5.0 (48.5)
What to watch for: The Cardinals are averaging seven sacks per game the past two weeks and that number isn't expected to be lower Saturday against the 49ers -- especially with the inexperienced C.J. Beathard behind center. Niners quarterbacks have been sacked 33 times this season. Look for another sack party from the Cardinals, especially from edge rusher Haason Reddick. -- Josh Weinfuss
Bold prediction: DeAndre Hopkins finishes with 10-plus catches and 100-plus yards for the second time against the 49ers this season. Hopkins had 14 catches for 151 yards in Week 1, and while those are gaudy numbers, it wouldn't surprise if Hopkins approached or surpassed them again this time. The Niners have allowed five wideouts to go for 100-plus receiving yards this season and Hopkins adds another to the tally. -- Nick Wagoner
Stat to know: Hopkins leads the NFL in receiving yards. No veteran player (i.e. non-rookie) since the 1970 merger has led the NFL in receiving yards in his first season with a team. Hopkins can become the first since Harold Jackson in 1969 for the Eagles.
Playoff/draft picture: The Cardinals clinch a playoff berth with a win and a Bears loss. They haven't made the playoffs since 2015, when they lost in the NFC Championship Game. The 49ers are eliminated from the playoffs, and they are projected to have the No. 12 pick, according to FPI, which gives them a 37.9% chance to pick in the top 10.
What to know for fantasy: Hopkins had two more catches than all of his teammates in the Week 1 meeting with San Francisco, catching 87.5% of his targets in the process (all other Cardinals: 57.1%). See Week 16 rankings.
Wagoner's pick: Cardinals 27, 49ers 20
Weinfuss' pick: Cardinals 37, 49ers 24
FPI prediction: ARI, 52.5% (by an average of 0.9 points)