TEMPE, Ariz. — No Saquon Barkley for the Giants when they face the 49ers on Thursday night in Santa Clara, Calif.

And it certainly looks as if no Barkley for the Giants in the Week 4 “Monday Night Football’’ game against the Seahawks Oct. 2.

Perhaps Barkley can make it back for the Oct. 8 game against the Dolphins.

That will be 21 days after Barkley sprained his right ankle in the closing minutes of the Giants’ astonishing 31-28 comeback victory over the Cardinals.

The immediate thoughts after that game was that Barkley suffered a low ankle sprain and on Monday that was revealed to be the case after Barkley had an MRI of the ankle.

ESPN reported it is an “ordinary’’ ankle sprain and that the timetable for a return is three weeks.

This means there will not be a heavyweight running back duel at Levi’s Stadium, featuring Barkley and Christian McCaffrey.

“Obviously we’ll miss him, he’s a huge part of what we’re doing,’’ Daniel Jones, fresh off a stunning second-half passing and running display, said Monday. “Guys will have to step up and it won’t be any one guy, it will be everyone elevating their play and stepping up. I’m confident we can do that.’’

Unfortunately for Barkley, this is a well-traveled road for him.

After a healthy rookie season, he missed three games in 2019 dealing with a right ankle sprain. That is what he is dealing with this time.

In 2020, he missed 14 games after tearing his right ACL. In 2021, he missed four games with a high left ankle sprain.

Barkley looked despondent in the locker room following the game.

“I think he’s doing all right,’’ Jones said. “He’s a mature guy. Obviously he’s disappointed, I feel for him on that. He’s gonna work hard to come back.’’

Barkley’s track record is that he attempts to shorten the recovery time and come back more quickly than expected.

He has said previously that, looking back, he returned to action too soon following his ankle issues.

Given that he is not under contract for the 2024 season, will he try to rush back this time?

Barkley went down with only 1:12 remaining in the game, fighting for extra push on a 2-yard run as the Giants were in the midst of coming back from a 21-point third-quarter deficit, setting up Graham Gano for his eventual 34-yard game-winning field goal.

The Giants, down 20 points at halftime, went into pass-mode in the second half, but Barkley did get the ball 10 times.

It was an unusually high snap count for Barkley — 66 of the 68 offensive plays. He finished with 63 rushing yards and caught six passes for 29 yards.

For the second consecutive game, Barkley had a pass come off his hands that resulted in an interception.

Barkley, though, had a rushing and receiving touchdown in the second-half surge.

And now he will miss time, again.

“Whatever it is, we’ll have a plan ready to go,’’ coach Brian Daboll said. “If he can play, he can play, and if he can’t we’ll have the other guys prepared and ready to go.’’

As far as the immediate plans, the Giants will have to lean on veteran Matt Breida at running back going against the rugged 49ers defense, with Gary Brightwell and rookie Eric Gray filling complementary roles.

“He’s extremely dependable,’’ Jones said of Breida. “He’s an explosive runner, he’s got the breakaway speed and he’s always doing the right thing. Just a guy you can count on to step up and play well. A guy you can definitely count on.’’

The 28-year old Breida, in two games this season, has only three rushing attempts (for 14 yards). He was with the Bills in 2021 when Daboll was the offensive coordinator in Buffalo.

“I’ve been with Matt for quite some time, he knows our system,’’ Daboll said. “He’s prepared every week as if he was the starter and that’s what they all need to do.’’

Barkley, 26, was not happy about the Giants placing the franchise tag of $10.1 million on him and he left it unsigned, forcing him to miss the entire spring offseason workout program.

Despite murmurings that he would take an aggressive stance and not report to training camp, Barkley agreed to a one-year deal worth up to $11 million and reported to camp on time.

His loss figures to be felt on both sides of the ball.

“It’s tough,’’ linebacker Bobby Okereke said. “[Defensive coordinator] Wink [Martindale] will always say he’s our best defensive player because when he’s on the field running the ball, we’re on the sideline. Saquon’s an incredible leader. This team is gonna miss him.’’