Bradford reinjured the knee he had surgery on last season and St. Louis had four other starters hurt in a 33-14 win over the Cleveland Browns on Saturday night.
He was examined on the bench and then 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."
"If you're going to sack Johnny, you've got to do that once," Sam said with a smile.
The former No. 1 overall draft pick missed nine games last season after tearing his left anterior cruciate ligament and having surgery, and St. Louis was counting on him to bounce back and have a big year.
Bradford's injury wasn't the only one sustained on a rough night for the Rams. The most serious appeared to be to cornerback Trumaine Johnson, who was carted off with a towel draped over his head in the second quarter. Johnson and tackle Michael Brockers were injured on the same play, but Brockers walked off under his own power.
"It was difficult for our team there to have those things happen," Fisher said. "I don't want the injuries to be the focus of this game. It's the third preseason game and we set our sights high and accomplished what we wanted to accomplish tonight."
Fisher took a cautious approach with the 26-year-old Bradford in training camp and delayed the QB's exhibition debut until last week against Green Bay. Bradford played well, completing 9 of 12 passes for 101 yards, and Fisher had hoped to give him more time against the Browns.
But he didn't get past the Rams' opening possession. After driving St. Louis to the Cleveland 12, Bradford, who wears a brace on his knee, dropped back and was hit high by Bryant as he threw an incompletion. Bryant didn't wrap his arms around Bradford, who turned and fell.
"It appeared to be just a hyperextension of the same knee," Fisher said. "We'll get you the information."
Coach Mike Pettine picked Hoyer this week over Manziel, the super-hyped first-round pick who didn't do enough in training camp to win the starting job. Manziel did provide some excitement in the second half, bursting from the pocket and diving into the end zone before celebrating his first rushing TD in his home debut with his trademark finger-rubbing gesture.
"It was a great first experience in the stadium," Manziel said. "To get a touchdown was incredible."
Hoyer finished 10 of 16 for 84 yards with one touchdown.
Manziel went 10 of 15 for 85 yards. In the fourth quarter, he was blindsided by Sam, the NFL's first openly gay player who is fighting to make the Rams' roster.
"I thought I played great in the fourth quarter," Sam said. "I think I got better today, which is very important. You have to do with the plays you have that you make sure you perform and I thought I came up big."
Copyright 2014 by The Associated Press