Bush injured his left knee on a punt return late in the first half. He reversed field on his run, which ended when he stepped out of bounds on the Carolina sideline. He seemed to pull up a bit and favor his left leg after that.
Bush missed practice earlier this week with swelling in his left knee, but the Saints said the injury was not serious.
Bush had 55 yards on nine carries, caught one pass for 5 yards, and had a 3.5 average on three punt returns against Carolina.
"Of course it's tough. He's a big-time playmaker," Brees said. "We're going to miss him, and I hope he's not out very long."
Information from the Associated Press was included in this report