This article is part of our NFL Picks series.
Arizona Cardinals vs. Philadelphia Eagles Betting Odds, Picks, and Predictions for Week 5
The Cardinals (2-2) look to build on what was arguably their best performance of the season, a 26-16 Week 4 win over the Carolina Panthers, when they host the Eagles (4-0), which will aim to remain the only undefeated team in the NFL after a come-from-behind 29-21 win over the Jaguars in Week 4.
Arizona Cardinals 
vs. Philadelphia Eagles 
for Week 5
Moneyline: Cardinals +198 (FanDuel Sportsbook)/ Eagles -225 (DraftKings Sportsbook)
Point spread: Cardinals +5.5 (FanDuel Sportsbook)/ Eagles -5 (PointsBet Sportsbook)
Total: Over 48.5 points (DraftKings Sportsbook)/ Under 49 points (PointsBet Sportsbook)
The Eagles' status as fairly heavy road favorites of as much as 5.5 points has expanded since the line was first released last week, when it opened at -4. The number went on to balloon all the way to -6 in the immediate aftermath of Week 4 before bettors started to invest in a Cardinals cover. That led to a dip to -5 and a constant toggling throughout the week between that figure and 5.5 through the rest of the week.
The total has seen some similar movement, albeit over a smaller range overall. The number opened at 48.5 and jumped up a point early in the week before eventually dipping back to 48.5 over the last 48 hours. The fact there are three Arizona offensive linemen sporting injury designations, including starting center Rodney Hudson, who's doubtful with a knee issue, and that Rondale Moore is also trending toward an absence due to his own knee injury certainly could be driving down Arizona's offensive expectations.
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Arizona Cardinals vs. Philadelphia Eagles Betting Picks This Week
As envisioned in this space last week, the Cardinals were able to handle a Panthers team they matched up well against in Week 4 without an inordinate amount of trouble. Arizona's elite run defense – the Cards have given up a minuscule 73.0 rushing yards per game in the last three contests – helped cap Christian McCaffrey's involvement on the ground and forced Baker Mayfield to try and win the game for Carolina, a predictably futile exercise.
Naturally, Arizona has no such luxury this week. While the Cardinals could well stymie Miles Sanders, who broke out with 156 total yards against the Jags in Week 4, in similar fashion, the deep Eagles offense can simply pivot to a highly dangerous passing attack.
Not only is Jalen Hurts playing at what is arguably an MVP level with 1,325 total yards and eight total touchdowns through four games, but both A.J. Brown and DeVonta Smith have already had outstanding individual efforts this season. Then, there's tight end Dallas Goedert, who finds himself in an enticing matchup against a Cardinals defense that's already allowed a 28-341-3 line to tight ends.
On the other side, the Cardinals and Kyler Murray in particular face the unenviable task of potentially facing the Eagles' talented defense with up to three missing offensive linemen and with a short-handed receiving corps yet again. A.J. Green will return this week from his knee injury, but Moore's likely absence leaves Murray in the same boat he was in for the first three games of the season.
The Eagles have allowed a modest 100.3 rushing yards per game, although at an elevated 4.7 RB yards per carry. Philly has allowed some breakaway runs that have influenced those numbers, but James Conner isn't exactly known for breaking into the second level, especially this season – he's averaging a career-low 3.2 yards per carry and hasn't recorded so much as a single run of at least 20 yards.
An inability to create any credible threat on the ground will leave Murray exposed to plenty of attention yet again, except this time it will be against a defense that already has five INTs and 16 sacks in four contests, and that's allowed just 177.0 passing yards per game and an NFL-low 56.4 completion percentage.
There's little question Murray and company will give it their all for as long as possible against a marquee opponent on their home field, but the talent disparity here will eventually be too much to overcome.
Cardinals vs. Eagles Best Bet: Eagles -5 (-110 at PointsBet Sportsbook)
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Arizona Cardinals vs. Philadelphia Eagles Prediction
Eagles 28, Cardinals 20
The Cardinals, as customary, will fight hard in this spot, but that will only get them so far with the potential pass protection issues they're likely to face and Murray's short-handed receiving corps. Ultimately, this is a game where a healthier, and in the present state of each club, more talented Eagles team eventually pulls away for a win of at least a touchdown thanks to a big performance from the team's air attack.
