St. Louis starting quarterback Sam Bradford re-injured his surgically repaired left knee in the first quarter against the Browns on Saturday night.
The Rams had four other starters hurt in the first half.
Bradford, who missed the Rams' final nine games last season after having a torn left anterior cruciate ligament repaired, went down after being pressured and hit high by defensive lineman Armonty Bryant.
As Bradford stayed on the ground for several minutes, Rams head coach Jeff Fisher came onto the field with trainers to check on his condition. Bradford, who is wearing a brace on his left knee, walked gingerly to the sideline, was examined by medical personnel behind the Rams bench before being escorted to the locker room for further medical tests.
Following the game, Fisher thought Bradford hyperextended his knee, but will wait for more tests on Sunday.
''I'm very optimistic for his quick return,'' said Fisher, who didn't provide many details of the injury.
Fisher said he spoke with Bradford, who was not available for interviews.
''He's fine, he's upbeat,'' Fisher said. ''We'll see.''
Bradford was playing his second pre-season game after making his exhibition debut last week against Green Bay. Fisher had hoped to play Bradford for most of the first half. He went 4 of 9 for 77 yards before leaving.
Bradford has made 49 career starts since he was drafted with the No. 1 overall pick by St. Louis in 2010. He was replaced by Shaun Hill.
The knock on Bradford is that he has not been able to stay healthy. He played in just 10 games in 2011.
St. Louis lost two other players in the opening quarter as defensive tackle Kendall Langford and guard Rodger Saffold went out with leg injuries.
Two more Rams were injured on the same play in the second quarter. Left cornerback Trumaine Johnson and defensive tackle Michael Brockers went down, but Brockers walked off under his own power.
Joyner's injury appeared to be serious. He was taken off the field on a cart, and several teammates wished him well before he was driven away.