The Rams have not officially confirmed the news, but head coach Jeff Fisher commented on the injury in his postgame press conference.
"It appears that we've lost Isaiah (Pead) with an ACL," Fisher said.
Pead suffered the injury while running back a kickoff in the first quarter. He took the ball down the left sideline, but went down untouched as his knee buckled while attempting a jump-cut.
Pead, the 50th overall pick in the 2012 NFL Draft, has posted 74 rushing yards and 94 receiving yards over his two seasons with St. Louis.