Isiah Pacheco and Brian Cook have been ruled out for the Chiefs’ Week 14 game

The Chiefs will not have one of their most important offensive players when they play the Bills on Sunday.

Running back Isiah Pacheco is one of four players left out by coach Andy Reid in his news conference on Friday.

Pacheco is dealing with a shoulder injury, the same shoulder he had surgery to repair in the offseason. Reid did not rule out spending time on injured reserve or safety Brian Cook, who was also ruled out with an ankle injury.

“They’re both being evaluated right now, so I’m not going to say anything about that,” Reed said. “But we’ll have to see that.”

Pacheco recorded 779 yards rushing with six touchdowns. He also has 33 catches for 209 yards with one TD.

Reid has confirmed that Clyde Edwards-Helaire will be No. 1 this weekend. He rushed for 140 yards on 40 touchdown carries. He’s also caught seven passes for 44 yards this season.

Jerick McKinnon (groin) is also headed into action after missing the last two games. He was a full participant in Thursday’s practice.

Left tackle Donovan Smith (neck) and linebacker Drew Tranquill (concussion) have also been ruled out for Week 14.

“Guys who step in have played. That’s the positive part about it,” Reed said. “So it’s not new territory for them when they get there.”

Waniya Morris is expected to take over at left tackle. But the team may have Nick Bolton back to play at fullback, where he was a full participant during this week’s training.

Bolton has not played since suffering a wrist injury in an Oct. 22 win over the Chargers. He will have to be activated off injured reserve to play.

Quarterback Patrick Mahomes was on the injury report with a pectoral issue, but was a full participant in practice and is not expected to be kept out of Sunday’s game.