New York Giants running back Saquon Barkley has been ruled out for Thursday's game against the San Francisco 49ers with an ankle injury.

Barkley injured his ankle in Sunday's comeback win over the Arizona Cardinals. He limped to the bench during the final drive of New York's 31-28 win and was later revealed to have sustained an ankle sprain.

ESPN's Adam Schefter reported Monday that Barkley was expected to miss three weeks after the results of his MRI. Head coach Brian Daboll declined Tuesday to rule him out for Thursday's game, calling Barkley a "quick healer." A day later, the Giants confirmed that they'll be without their Pro Bowl running back in a tough matchup against the 49ers.

Barkley, 26, has tallied 155 yards from scrimmage and two touchdowns while averaging 3.9 yards per carry through two games. The Giants struggled mightily in a season-opening 40-0 loss to the Dallas Cowboys. Then they fell into a 20-0 halftime hole against the Cardinals before scoring 31 points in the second half to rally for the win. Barkley scored both of his touchdowns in the second-half comeback.

His absence Thursday is a significant blow against a 2-0 49ers team that looks like one of the best teams in the NFL two weeks into the season. The Giants will lean on veteran Matt Breida in his absence.

The injury's likewise a tough blow for Barkley, who's playing this season on a one-year deal after failing to secure a long-term contract from the Giants in the offseason. Barkley's long proven himself as one of football's most dangerous offensive weapons, but was hoping again to secure a long-term contract with his play this season amid an increasingly difficult market for NFL running backs.