The team announced Friday that Kamara and Cook were ruled out for the Week 7 contest. The Saints also will be without wide receiver Tre'Quan Smith (ankle) and defensive end Trey Hendrickson (neck).
Kamara, who has been dealing with ankle and knee injuries, didn't practice this week after being injured during Sunday's game against the Jacksonville Jaguars. Cook, who has an ankle injury, also failed to practice this week.
Veteran backup tailback Latavius Murray, who was a starter with the Oakland Raiders and Minnesota Vikings, will replace Kamara in the starting lineup. Veteran tight end Josh Hill is expected to see increased snaps in Cook's absence.
Murray, 29, has 3,836 rushing yards, 950 receiving yards and 35 touchdowns in his NFL career. He was a Pro Bowl selection with the Raiders in 2015, then split reps in the Vikings' backfield for the last two seasons.
Through six games this season, Kamara leads the Saints with 649 total yards from scrimmage. Cook recorded seven receptions for 78 yards and two touchdowns in the last two weeks.