Cardinals at Giants (-3.5/50), 1 p.m. ET, FOX: Clouds are expected to threaten throughout this game and rain may be a part of the festivities throughout the day. That means conditions won’t be favorable for the return of Giants RB Saquon Barkley and Cardinals’ All-Pro corner Patrick Peterson, although the presumption is that it makes the defensive star’s life easier. The Giants won’t have Sterling Shepard back from concussion protocol, so Peterson will get to focus on a familiar face with Golden Tate emerging as rookie Daniel Jones’ preferred top target.
No. 1 pick Kyler Murray has led the Cardinals to back-to-back wins and will have RB David Johnson in the mix despite an ankle issue, so look for he and Chase Edmonds to get a heavy workload as the team’s only available backs. Johnson reported that his back is feeling much better after impacting his production earlier this season. He’s combined for over 100 yards in three straight games. Speedy Christian Kirk is still rehabilitating his ankle injury and will likely miss one more game since he’s not completely ready to return.
Texans at Colts (-1.5/46.5), 1 p.m. ET, CBS: The winner of this one will be nicely positioned atop the AFC South, making this one of the day’s most important games. Houston is currently the only team in the division with a positive point differential, posting wins in four of five. The Texans have been beaten by a last-second field goal in New Orleans and came up just short at home against the Panthers, so they’ve been in every game they’ve played, just like the Colts. Indy has suffered an OT loss at the Chargers and fell to the Raiders at home. Like Houston, it too comes off an upset win over the Chiefs, but also had the benefit of watching last week’s Texans’ win from the comforts of home since they were on a bye.
The Texans are going to have to come issues on their offensive line, a season-long theme despite their success, because center Greg Mancz will miss a third straight game and rookie tackle Tytus Howard has been ruled out. The first-round pick has started every game, so we may see Houston run it more since he’s stood out as a pass blocker. Indianapolis guard Quenton Nelson landed on the injury report but is expected to play, so the Colts will again have their standout offensive line together. They’ve played every snap this season, opening holes for Marlon Mack and helping keep Jacoby Brissett clean. The Colts will be dealing with a Texans’ secondary that should have corner Johnathan Jospeh and safety Tashaun Gipson back from hip injuries, but won’t have corner Bradley Roby. Indianapolis will have top LB Darius Leonard back following a three-game absence.
Jaguars (-4.5/44) at Bengals, 1 p.m. ET, CBS: The Gardner Minshew Experience has hit a rough patch, but he’s proven he’s nothing if not resilient considering his preseason was so awful and he bounced back nicely from that. We’ll see how he handles getting back on track after finishing 14-for-29 for 163 yards and a pick in a 13-6 loss to the Saints, but it may help the cause that starting corners Turtle Jackson and Dre Kirkpatrick are sidelined. DE Carl Lawson is out and Carlos Dunlap has been downgraded to doubtful, so Minshew has a chance to put up some numbers against a depleted unit. WR Dede Westbrook has been a disappointment but should be able to play through a shoulder injury, which is good news since the Jags will already be missing Marqise Lee (foot) and tight ends James O’Shaughnessy (ACL) and Geoff Swaim (concussion).
The Bengals have had issues getting anybody blocked up front, which could lead to another long day for Andy Dalton as he remains top target without A.J. Green. Tackles Andre Smith and Cordy Glenn have both been ruled out, as has guard John Miller. DT Ryan Glasgow will be back out there, but remaining winless hasn’t exactly expedited the recovery period for a lot of key guys. Cincinnati is 0-2 against the spread at home but covered in last week’s loss at Baltimore thanks to a late score. The Jags have trailed for most of their three games on the road, winning only at Denver on a last-second field goal.
Rams (-3/54) at Falcons, 1 p.m. ET, FOX: If L.A. falls under .500, Jared Goff is going to come under fire, so it’s fortunate that Blake Bortles is his backup since it’s not like the fan base will exactly be clamoring for a change. Make no mistake, although the offensive line has had its issues, the Rams being unable to score points falls on the shoulders of their quarterback and his errant passes. Although Malcolm Brown is out with an ankle injury, the offense gets Todd Gurley back from his quad issue and should have better balance to try and get back on track against a Falcons defense that has given up at least 20 points in every game this season, surrendering 43.5 points over the past two. Corner Desmond Trufant is out and safeties Jonathan Cyprien and Keanu Neal have been lost, so if Goff can’t get loose here, the Rams will be in a bind.
Falcons head coach Dan Quinn has gotten a vote of confidence from owner Arthur Blank and his players over the past few weeks, but sustaining another loss in front of what would be a vocally displeased home crowd could be the final straw for him. Jalen Ramsey will look to pay immediate dividends in clocking in for Julio Jones duty with Aqib Talib and John Johnson both out injured. Los Angeles has never been under .500 under Sean McVay, last sporting a losing record after John Fassel closed out the 2016 season following Jeff Fisher’s firing. This is a huge game for the entire organization.
49ers (-10/40) at Redskins, 1 p.m. ET, FOX: Washington isn’t in condition to knock off the NFC’s lone unbeaten, but hey, they’re in town, so why not try? It’s going to take another big game from WR Terry McLaurin, a talented rookie who has dominated opposing defensive backs but will have to deal with a secondary that has allowed a single QB to pass for over 200 yards and just one 100-yard receiver. Adrian Peterson had 100-yard rushing day against Miami but is no longer the type to loosen up a defense, so it could be a long day for Case Keenum as he looks to get interim head coach Bill Callahan a second straight win that would be the Redskins’ first set of back-to-back wins in nearly a calendar year.
The 49ers haven’t started 6-0 since 1990 and will have to overcome rainy conditions and the continued absence of tackles Mike McGlinchey and Joe Staley in addition to fullback Kyle Juszczyk. Fortuntately, George Kittle is cleared to work despite a groin strain and set to go, which should mean the offense should remain effective despite also having to replace rookie playmaker Deebo Samuel (groin). The ‘Skins have major issues in the back end of their defense with Josh Norman a game-time decision (groin) and LB Josh Harvey-Clemons and safety Deshazor Everett out. If the weather in Landover holds up enough where Jimmy Garoppolo gets time to throw downfield, Marquise Goodwin could have a big game.
Chargers at Titans (-2.5/42), 4:05 p.m. ET, CBS: Marcus Mariota will watch from the sidelines as Ryan Tannehill tries to complete the process of taking his job in Nashville. The former Dolphins starter entered last week’s disappointing 16-0 loss in Denver and finished 13-for-16 with an interception, which are still better numbers than the former No. 2 overall pick put up. A Derrick Henry TD run in the third quarter of a home loss to the Bills on Oct. 6 are the team’s only points over the past 10 quarters and TE Delanie Walker potentially missing this game won’t help matters. Tennessee’s defense has been fantastic most of the season in keeping the Titans in games and winning a pair outright, but attrition is a factor with LB Sharif Finch out and counter part Jayon Brown doubtful. Pass rusher Cameron Wake is questionable too, but the secondary should have standout safety Kenny Vaccaro to help deal with the Chargers’ weapons.
Philip Rivers found Hunter Henry for a pair of scores once the Chargers already trailed 24-0, but the offense was to blame for putting the team in a huge hole against Pittsburgh and hasn’t looked right since Melvin Gordon returned to action. That’s not to say the running back is to blame, but Ken Whisenhunt has had trouble incorporating him back in the fold. L.A.’s defense will have linebackers Denzel Perryman and Thomas Davis in place but have ruled out nose tackle Brandon Mebane (knee) and DT Justin Jones (shoulder) while listing Melvin Ingram as doubtful. That will likely be good news for Henry, Tannehill and a Titans offense looking to get on track.
Ravens at Seahawks (-3/48.5), 4:25 p.m. ET, FOX: Russell Wilson is now a 7-to-4 favorite to win the NFL MVP per Westgate following Patrick Mahomes’ Thursday night injury, ranking ahead of Houston’s Watson. The Seahawks’ star leads the league in passer rating, touchdowns and game-winning drives and hasn’t been picked off. The Ravens have struggled against the top passing attacks they’ve seen thus far, giving up 37.5 points in losses to the Chiefs and Browns, so they’ll need their best effort in holding up here. Safety Tony Jefferson tore his ACL to open the month and corner Jimmy Smith has been out for weeks, so the availability of corner Maurice Canady is particularly important since he’s dealing with a hamstring issue. Anthony Averett is dealing with an ankle issue.
Rain is likely to be a part of the action in Seattle at some point, which could actually favor the slippery Lamar Jackson since it will be more difficult for the Seahawks’ pass rush to get to him. Unfortunately, top playmaker Marquise “Hollywood” Brown is unlikely to play after not practicing all week, so Willie Snead and Miles Boykin will get the majority of snaps in what will likely be a run-heavy attack designed in part to keep the ball out of Wilson’s hands. Seattle has its own issues on the offensive line and probably won’t have its desired combination up front for the next few weeks. Tackle Duane Brown hasn’t practiced all week, while guard D.J. Fluker is dealing with a hamstring injury. The Seahawks have to replace tight end Will Dissly too, likely turning to Luke Willson. DE Ziggy Ansah, DT Quintin Jefferson and safety Bradley McDougald are all questionable too.
Saints at Bears (-4/37), 4:25 p.m. ET, FOX: With Alvin Kamara sitting due to an ankle sprain and Drew Brees still not back from his thumb injury, New Orleans will have to manufacture offense against one of the league’s top defenses in a tough atmosphere. Following a warm day in Jacksonville and a pair of games in the Superdome, the Saints hit the road to deal with temperatures in the 50s in addition to Khalil Mack. Considering Teddy Bridgewater comes off a disappointing outing in Jacksonville, I’d expect to see Taysom Hill play more than he has and the ball to be in the air less than it normally is under Sean Payton. While that may ultimately have you running to the counter to ride the Bears at home, Mitchell Trubisky’s return from a shoulder injury carries its own risk. The second-year QB hasn’t exactly lit it up when healthy and a defense that had looked dominant throughout the first month struggled overseas in losing to the Raiders. Although DE Akiem Hicks has now been ruled out for most of the regular season, DT Bilal Nichols is expected back to help fill out the defensive front.
The Bears’ offensive line suffered a big blow with guard Kyle Long landing on IR after attempting to play through a hip issue. Matt Nagy should have a few wrinkles in coming off a bye but can’t get cute given all the moving parts on the Bears’ offense. New Orleans will attempt to survive via the legs of Hill and Latavius Murray in addition to Michael Thomas’ ability to live up to his can’t-guard-Mike Twitter handle.