Backup Joe Flacco will make his third start of the season for the winless Jets (0-8).
The Jets were optimistic at the start of the week that Darnold, who aggravated the previously injured shoulder last Sunday, would be able to start. After sitting out practice Thursday as a precautionary rest day, he returned Friday and didn't feel right, coach Adam Gase said.
Gase said Darnold will be listed as doubtful, but he made it clear that Flacco will get the nod "unless something strange happens."
The Jets are 0-8 when Darnold doesn't start, dating to his rookie year, 2018.
Darnold hurt the shoulder -- a sprained AC joint -- on Oct. 1 against the Denver Broncos, causing him to miss two games. He returned for two games, then took a hit late in a 35-9 loss to the Kansas City Chiefs.
"Obviously, he was going to do everything he could to go in this game," Gase said. "As practice went on [Friday], he felt like there were some throws he wasn't comfortable with. When he threw them, he didn't feel like he got the right velocity that he wanted on the ball."
Darnold told the coaches "it didn't feel the way he felt it should," Gase said. "I'm glad he did that. That's what I think we needed, was that communication back. I know it's devastating for him because he's always been able to throw the ball the way he feels he needed to, and I think [Friday] was the first time he felt it did not feel the way he wanted it to."
Speaking to reporters Friday after practice, Darnold's mood seemed down as he discussed his prospects for Monday night. He was noncommittal, saying he needed to take it day by day -- a big change from his upbeat demeanor on Monday. Flacco, who struggled in his two previous starts, should be prepared because he took most of the reps for the week. Darnold wound up getting only half the reps on Friday.
Gase declined to speculate on whether this will be a long-term injury. After the Patriots (2-5), the Jets have a bye. They don't play again until Nov. 22 at the Los Angeles Chargers. By sitting Monday night, Darnold will have a three-week rest between games.
This is another setback for the young quarterback, who hasn't had anything go right this season. Aside from the shoulder injury, he has struggled to spark the offense, which has managed only seven touchdowns in eight games.
Darnold has gone three straight games without a touchdown pass and nine straight without more than 230 yards in a game, dating to last season. He ranks 29th out of 31 qualifying quarterbacks in Total QBR (40.0).
His future appears uncertain, as the Jets will have a high draft pick -- perhaps No. 1 overall -- and could be in position to select a top quarterback.
In other injury news, wide receivers Jamison Crowder (groin) and Breshad Perriman (concussion) are expected to play. They will join rookie Denzel Mims, marking the first time their starting three receivers will play together.
Now they're missing their quarterback.
"I think it sucks for [Darnold]," Gase said. "He's been waiting for those three guys to be together since the beginning."
Even though he never had a shoulder injury, Flacco said there's no doubt it has impacted Darnold in recent weeks.
"I mean, come on, yeah," he said. "You just take a look at his shoulder. I think he's done an unbelievable job of playing through it and dealing with it, but it has to take its toll on you. It's definitely going to have some effect on that ball. ... It's a big-time limiting factor."