Freeman missed practice all week, including Friday. Rookie Tevin Coleman is expected to start at running back.
Coach Dan Quinn said kicker Matt Bryant (right quadriceps injury) and wide receiver Leonard Hankerson (hamstring) also will miss the game. The Falcons signed Shayne Graham on Thursday to fill in for Bryant.
The loss of Freeman is a major blow for Atlanta (6-4), which has lost three straight and four of five following a 5-0 start. The Falcons are in danger of falling behind in the NFC wild-card race.
Entering Week 12, Freeman ranked second in the NFL with 1,184 yards from scrimmage, only 5 yards behind teammate Julio Jones, and fifth with 764 yards rushing. His nine rushing touchdowns lead the league; no other player has more than seven.
Quinn said Coleman should benefit from a full week with the starters in practice.
"He's had a really good week," Quinn said. "There's a lot you can learn when you get more reps and you get more game time. That was certainly the case with him. We have so much trust and belief in him. We know he has the speed to break the big ones."
The Falcons have had a full week to tailor their game plan to emphasize Coleman's speed, too.
"Whether it's inside zone or outside zone, it's the speed ... one cut, put his foot in the ground and go," Quinn said. "That part of it we know. That's what we've seen. That's what we expect of him."
Quinn said Freeman has not completed the NFL concussion protocol. He said Freeman is "doing really well" and attended a team meeting Friday.
Coleman started the first two games of the season. He had season-high totals of 20 carries for 80 yards in Atlanta's 26-24 win over Philadelphia to open the season.
Atlanta's running game took off when Freeman took over with 141 yards rushing and three touchdowns in a Week 3 win over the Cowboys.
Freeman had three carries for 43 yards before leaving last week's 24-21 loss to Indianapolis with the concussion. Coleman managed only 48 yards on 17 carries.
This will be Atlanta's first game without Bryant, 40, since he signed with the team late in the 2009 season. His 162 field goals rank second in team history behind Morten Anderson's 184.
Graham, 37, has kicked for nine teams. He made 19 of 22 field goals for the Saints last season.
Hankerson had four catches for 36 yards, including a 3-yard touchdown pass from Matt Ryan last week before leaving in the fourth quarter. It was his return after missing two games with a hamstring injury.