The New York Giants have reportedly ruled out running back Saquon Barkley and left tackle Andrew Thomas for Thursday night's game against the San Francisco 49ers, according to Ian Rapoport of NFL Network.

Saquon Barkley injured his ankle in Sunday's game against the Arizona Cardinals, and while Giants coach Brian Daboll did not rule him out yesterday, it was a long shot for him to play. Andrew Thomas missed the Cardinals game due to a hamstring injury that was suffered in Week 1 against the Dallas Cowboys, so the Giants will be without their All-Pro left tackle against the dangerous 49ers pass rush.

Outside linebacker Azeez Ojulari and guard Ben Bredeson were also ruled out for the game, according to Rapoport.

Azeez Ojulari is out for the second straight game with a hamstring injury, while Ben Bredeson is missing the game after suffering a concussion during Week 2's game against the Cardinals.

The absence of Barkley and Thomas are the biggest ones, but Ojulari and Bredeson being out is significant as well.

The Giants were going to be significant underdogs in this game against the 49ers regardless, but it will be a tougher task now without these key players. The absence of Thomas is arguably bigger than Barkley's. He is an All-Pro tackle who protects Daniel Jones' blind side. Now, Nick Bose will have a chance to rush the passer against either a backup left tackle or right tackle Evan Neal, who has struggled mightily.

It will be intriguing to see how the Giants manage without these key players.