Gurley, who is dealing with inflammation in his left knee, was held out for a series in the third quarter of last week's 30-23 loss to the Philadelphia Eagles. He has not practiced all week.
With Gurley inactive, newcomer C.J. Anderson figures to lead the Rams' backfield with second-year pro Justin Davis serving in a change-of-pace role for Los Angeles (11-3). The Rams, who have clinched the NFC West, face the division-rival Cardinals (3-11) and San Francisco 49ers (4-10) to wrap up the regular season.
"We're not going to do anything that isn't smart for Todd," Rams head coach Sean McVay said on Friday. "I thought he said it perfectly yesterday. It's a team effort -- trusting how he feels, what our doctors say, and what is best for our football team. The one thing that is really good about him is he's not going to do anything to put himself in harm's way. He knows his body. We're certainly not interested in doing anything of that nature. But we're going to give ourselves about that 48 hours that we do have until we kickoff on Sunday."
Gurley rushed for 48 yards and two touchdowns and caught 10 passes for 76 yards in the setback against the Eagles.
The 24-year-old Gurley has rushed for 1,251 yards and has 59 receptions for 580 yards this season en route to recording a league-best 21 touchdowns (17 rushing, four receiving).
Gurley is coming off a monstrous season in 2017 in which he led Los Angeles to the NFC West title. He became the first Rams player to win the Offensive Player of the Year award since Marshall Faulk in 2001.
The former University of Georgia product led the NFL in touchdowns (19), points scored among non-kickers (114) and scrimmage yards (2,093), in addition to finishing second in rushing yards (1,305). He also topped the league's running backs in receiving yards with 788 and his average of 6.1 yards per touch was the best in the NFL.