The New England Patriots will likely have to turn to a rookie at quarterback after their win over the Miami Dolphins proved a costly one.
Games were won and lost Sunday, but the 2016 NFL season is already becoming one of attrition, with Jimmy Garoppolo and Adrian Peterson headlining a substantial injury list.
New England Patriots quarterback Jimmy Garoppolo left their 31-24 win over the Miami Dolphins in the second quarter after throwing for 234 yards and three touchdowns. He sprained the AC joint in his right shoulder and likely will be unable to play in Thursday night's game against the Houston Texans - who beat the Kansas City Chiefs 19-12.
Meanwhile Minnesota Vikings star Peterson was one of many big name running backs to go down hurt as he left their 17-14 win over the Green Bay Packers with a right knee injury.
The San Diego Chargers lost Danny Woodhead with what appeared to be a serious right knee injury as they crushed the Jacksonville Jaguars 38-14 and Miami's Arian Foster suffered a groin injury.
Carolina Panthers tailback Jonathan Stewart departed their 46-27 win over the San Francisco 49ers with a hamstring issue, and a similar problem saw Doug Martin leave the Tampa Bay Buccaneers' 40-7 loss to the Arizona Cardinals in the second quarter.
Denver Broncos pass rusher DeMarcus Ware suffered a fracture ulna bone as the defending champions beat the Indianapolis Colts 34-20.
Perhaps the scariest injury happened to New Orleans Saints cornerback P.J. Williams, who was taken to a New Jersey hospital after getting hit in the head twice on the same play.
Williams was knocked unconscious in the first half of the 16-13 loss to New York Giants and the game was halted for several minutes. He was immobilised and placed on a backboard before being carted off the field.
Though he suffered a concussion, Williams was able to move his fingers and toes and the Saints are optimistic he avoided serious injury.
The Atlanta Falcons' first win came in a 35-28 defeat of the Oakland Raiders, the Los Angeles Rams recovered from their Monday night horror show to stun the Seattle Seahawks 9-3 and the Pittsburgh Steelers overcame the Cincinnati Bengals 24-16.
Elsewhere, the Dallas Cowboys held off the Washington Redskins 27-23 and the Baltimore Ravens beat the Cleveland Browns 25-20, while the Tennessee Titans triumphed 16-15 over the Detroit Lions with a fourth-quarter turnaround.
DEFENSE WINS THE DAY
The Giants and Saints were surprisingly locked into a defensive struggle and the game's first touchdown was scored by the New York defense as cornerback Janoris Jenkins returned a blocked field goal 65 yards.
Isaiah Crowell's 85-yard touchdown run in the first quarter is the longest touchdown so far in the young season and the second-longest run in Browns history.
ALL DAK AND MORE
The Cowboys beat the Redskins thanks in part to 292 passing yards and a six-yard rushing touchdown by rookie quarterback Dak Prescott. Prescott completed 22 of his 30 passes, including seven to top wideout Dez Bryant for 102 yards.
Philip Rivers paced the Chargers offense, which showed no ill effects following Woodhead's injury in the drubbing of the Jaguars. He went 17 of 24 for 220 yards and four touchdowns. Already without top receiver Keenan Allen for the season, Travis Benjamin filled the pass-catching void with 115 yards on six grabs and a pair of touchdowns.
Patriots running back LeGarrette Blount ran for 123 yards and a touchdown against the Dolphins, including a 26-yard run early in the fourth quarter as he hurdled Dolphins cornerback Byron Maxwell.
IT'S A BREES
With 263 passing yards Sunday, Saints quarterback Drew Brees moved past Dolphins Hall of Famer Dan Marino for third place on the all-time passing yards list.
While leading the Panthers to a rout of the 49ers, Carolina quarterback Cam Newton overtook Jake Delhomme for the most touchdown passes in team history by throwing four on Sunday.
Ravens receiver Steve Smith caught three passes for 64 yards in the win over Cleveland to leapfrog Hall of Famer James Lofton for 10th place on the NFL's all-time receiving yards list.
NORMAN RIPS DRUG POLICY
Redskins cornerback Josh Norman is not a fan of the NFL's new post-game drug testing policy, and he did not mince words when targeted for a random exam following the loss.
"I don't like how the NFL has us drug test right after the game," Norman said. "I don't understand that. It's crazy. I don't have anything left in the tank, yet they want you to drug test. It's crazy. I don't understand it. What's a day going to do? 24 hours? It's stupid."
New York Giants coach Ben McAdoo had a pretty good reason for having his team kneel on the ball three times at the two-yard line after Victor Cruz's 34-yard reception with under two minutes remaining.
"We didn't want to give Drew [Brees] the ball back," McAdoo said of the decision to have Josh Brown kick a 23-yard field goal as time expired. "That simple. He's a heck of a player, a future Hall of Famer. If you can end the game with a kick, you want to end the game."
NEXT MAN UP
All the injuries point to the age-old sports cliche: next man up. With Tom Brady still two games from his season debut, the next man up for the Patriots is Jacoby Brissett, who would become the first New England rookie quarterback to start a game since Drew Bledsoe in 1993 if Garoppolo is unable to play on short rest.