The Kansas City Chiefs will be without one of their biggest offensive weapons on Sunday.

Running back Isiah Pacheco has been ruled out of the Chiefs' home matchup against the Buffalo Bills due to a shoulder injury, the team announced on Friday. Pacheco, who suffered a shoulder bruise in the same shoulder he had surgery to repair a torn labrum in the offseason, didn't practice all week before being ruled out.

The second-year running back has handled 57.8% of Kansas City's rushing attempts this season (176 carries) and has compiled 779 rushing yards and six rushing touchdowns through 12 games (11 starts). Clyde Edwards-Helaire, who is third in Chiefs' carries (14%) behind Pacheco and QB Patrick Mahomes, will serve as the team's lead running back on Sunday.

"(Edwards-Helaire) is the number one guy," head coach Andy Reid said in a press conference Friday. "He’s done a great job. Clyde’s a good kid. The chances he’s had to play, he’s done well." 

Alongside Pacheco, safety Bryan Cook (ankle), OL Donovan Smith (neck) and LB Drue Tranquill (concussion) have also been ruled out vs. the Bills. Reid did not provide a timetable for Pacheco and Cook's return to the field.

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"We’ll see," Reid said when asked if Pacheco and Cook could land on the injured reserve with their injuries. "Both of them are kind of being evaluated right now, so I won’t say anything on that, but we have to see."

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Bills QB Josh Allen (right shoulder injury) and Mahomes (pectoral) were listed on their team's respective injury reports, but both are expected to play on Sunday after logging multiple full practices this week.

Both teams are coming off a loss and desperately need a win: The Bills (6-6) lost 37-34 in overtime to the Philadelphia Eagles in Week 12 before their bye week, and the Chiefs (8-4) lost 27-19 to the Green Bay Packers last week.