Coach Steve Spagnuolo says Clayton has had issues with both knees and was in pain earlier in the practice week. Smith sustained a concussion and a neck injury Oct. 23 against Dallas. Clayton and Smith became the 12th and 13th Rams players, respectively, now on the IR list.
Clayton had reconstructive knee surgery last October and has struggled with Achilles tendinitis since being activated off the PUP list, playing sparingly in two games. He had three catches for 26 yards last week against Seattle.
The Rams also re-signed wide receiver-kick returner Nick Miller.
Smith did some work on the bike Monday, but then had to shut it down.
"We just thought it was the right thing to do now and here's the reason why. When you really look at it, he's getting close but he's not there," Spagnuolo said after practice. "He hasn't done anything for a month. The concern got to be if we waited another week or two weeks, and try to get him ready to go, are we doing the right thing for the player in that you don't do anything for five weeks and then you rush him out there?
"We're trying to be smart about it. He'll fight through this thing like he did a couple of years ago and we'll get him back and he'll be ready to roll."
The Rams (2-8) will host the Arizona Cardinals (3-6) on Sunday and one of the big goals is to protect quarterback Sam Bradford. In his second season, Bradford has been sacked 31 times for 205 yards in losses. His quarterback rating is 70.9.
Rodger Saffold, the left tackle, tore a chest muscle lifting weights last week and was placed on injured reserve. Backup Mark LeVoir took his starting spot last Sunday against Seattle and sustained a similar pectoral muscle injury that will have him out up to four weeks.
When LeVoir when down, undrafted rookie Kevin Hughes of Southeast Louisiana took over. Hughes was promoted from the practice squad the day before the game when Safford went on IR.
Chris Clemons, Seattle's top pass rusher, made Hughes' NFL debut one to forget. Hughes allowed 2½ sacks, two quarterback hits and a quarterback hurry against Clemons.
Backup Adam Goldberg has been at right tackle since Smith went down.
The Rams also signed offensive tackle Thomas Welch to the roster Tuesday from the Buffalo practice squad. Welch was with New England to begin the season and made one start for the Patriots.
"He's a guy that the personnel department had their eyeball on," Spagnuolo said about Welch. "He's been in the system, knows the terminology and the verbiage and whatnot, so that's a bonus. And he's a big guy."
Spagnuolo has options to mix and match. Guard Harvey Dahl has played tackle before and Brown has played at guard.
"We're going to have five guys line up on the OL and away we go," said Spagnuolo, declining to reveal who was going to play where Sunday.
Running back Steven Jackson acknowledged the juggling on the offensive line affects his timing. The three-time Pro Bowler had a string of three consecutive 100-plus yards gained snapped in last week's loss to Seattle.
"It affects it a little bit. That's why I have to try and get as many reps as I can throughout the week with those guys," Jackson said. "(I) try to get a feel for how things are going to flow, how things are going to work when we have pulling guards or pulling tackles in the game. The mesh and all of that will happen over repetition.
"Injuries occur, mismatches with the offensive line has happened before, nothing that I haven't had to deal with. It's just more so getting the chemistry and trying to get a feel for how the guys are going to work together."
Offensive coordinator Josh McDaniels noted while the shuffling of players along the line is necessary because of injuries, the staff balances such issues by using its best guys, but not displacing any one.
"That's always a part of the equation, no question about it," McDaniels said. "I don't think there's really any easy way to go about doing that because no matter what you choose to start the game with, you're always one injury away from shuffling more anyway.
"We're going to ask some other guys to do multiple things because we have to. We're at that point now where you're going to have potentially to play a guard at tackle, potentially play a center at guard, swing guys left and right. And then if something does happen in the game, there's no question there's going to be some moving parts and pieces within the four quarters then, too. They've accepted the challenge and the burden that we have. It's normal, every team goes through it. We've got to deal with it this week."
Information from The Associated Press was used in this report.