The Giants won’t have their best offensive lineman and their best skill player against arguably the NFL’s best team Thursday night.

Running back Saquon Barkley and left tackle Andrew Thomas have both been ruled out for Thursday’s road matchup against the 49ers.

Barkley will miss the game with a sprained ankle injury suffered in the Week 2 win over the Cardinals.

Giants head coach Brian Daboll — in what now appeared to be a bit of sportsmanship — left open the possibility Wednesday that Barkley could play Thursday.

Thomas will now miss his second straight game with the hamstring injury suffered in the season-opening 40-loss to the Cowboys.

The Giants now will hope that both Barkley and Thomas can return for their Week 4 matchup on “Monday Night Football” against the Seahawks at MetLife Stadium.

Stream the game live on Thursday night on Amazon Prime Video

Offensive lineman Ben Bredeson (concussion) and linebacker Azeez Ojulari (hamstring) are also out Thursday, while linebacker Micah McFadden (neck) and receiver Wan’Dale Robinson (knee) are questionable.

If Robinson plays, it will be his season debut.