The quartet of Kansas City Chiefs starters also missed practice Wednesday.
Pacheco, the team's leading rusher and a battering ram for the offense, might be the most-significant absence if he can’t go on Sunday.
Jerick McKinnon, who missed the last two weeks with a groin injury, was a limited participant Wednesday at practice. He is No. 2 behind Pacheco on Kansas City’s depth chart at running back, so there already were injury concerns at the position.
If Pacheco isn’t able to play, former first-round pick Clyde Edwards-Helaire would be in line for a bigger role.
The Chiefs also have two running backs, La’Mical Perine and Deneric Prince, on the practice squad who have been elevated for games this season.
“‘Pop' (Pacheo) has been phenomenal for us all year," offensive coordinator Matt Nagy said. "He brings that energy, that physicality. He’s really starting to become a leader, as well. But the other guys in that room have done a good job all year long of starting to complete that room and joining him. It’s really just a next-man-up mentality.”
Running back Keaontay Ingram also is on the practice squad.
Defensively, Tranquill suffered a concussion and Cook suffered an ankle injury, which the Chiefs say is a sprained ankle, during the second half Sunday at Green Bay.
Smith had been dealing with a neck stinger, according to Kansas City coach Andy Reid. He missed a drive two weeks ago at Las Vegas and during the first half against the Packers, but tried to battle through.
Rookie fourth-round tackle Wanya Morris replaced Smith on both drives and played the entire second half at Green Bay.
Reid said he’s confident in Morris, if he has to start Sunday’s game against the Buffalo Bills at GEHA Field at Arrowhead Stadium.
Tranquill, who leads the Chiefs in tackles, stepped in as the starting middle linebacker for three games in September after Nick Bolton suffered a calf injury.
Tranquill returned to a starting role after Bolton suffered a dislocated wrist and needed surgery in late October.
Bolton has returned to practice, opening a 21-day window for him to return from injured reserve and rejoin Kansas City’s active roster.
He was a full participant Wednesday at practice, a hopeful sign that he may be available against the Bills.
“He boosts me,” defensive coordinator Steve Spagnuolo said of Bolton. “He’s an energy-giver. I know the guys feel that in the huddle.”
Core special-teams player Jack Cochrane stepped in with Bolton and Tranquill unavailable last week.
The Chiefs have until Saturday to activate Bolton and make a corresponding move to free up space on the 53-man roster.
Cook was replaced by veteran Mike Edwards, who would be in line to start if the second-year safety isn’t able to play against Buffalo.
Kansas City also signed former Mizzou standout Tyree Gillespie to the practice squad on Tuesday.
Gillespie was drafted by Las Vegas and played last season for Jacksonville. He’s also spent time with Tennessee and Houston in his three-year NFL career.