Coach Ron Rivera said Monday that Smith was "highly doubtful" but the overall news was good. Smith is considered week to week with a sprained posterior cruciate ligament.
"It's very optimistic as we go forward," Rivera said.
Should the Panthers (11-4) beat Atlanta, they would win the NFC South and have a first-round playoff bye. That would make Smith's likely return a home playoff game in three weeks.
Rivera said Ted Ginn Jr. likely will slide into Smith's role against Atlanta and rotate with Domenik Hixon, who caught a 14-yard touchdown pass from Cam Newton with 23 seconds left in Sunday's 17-13 win over New Orleans.
"It's time for other guys to step up, and they're ready," offensive coordinator Mike Shula said.
Rivera said Smith was in good spirits on Monday after the MRI.
"He's very optimistic," he said of the team's all-time leading receiver. "I said, 'Is it good news?' He said, 'Well, it doesn't feel very good right now, Coach. But you know me.' We do know Steve. Steve is tenacious, and he'll do everything he can [to get back]."
Smith said he felt the knee pop as he attempted to jump for a high pass from Newton on a third-down slant pattern. The five-time Pro Bowler stayed down for several moments before walking off the field under his own power.
After being checked out on the sideline, Smith was taken to the locker room. He attempted to return, but after struggling to run a 10-yard route, he was taken back to the locker room and ruled out.
Rivera wasn't surprised Smith tried to return.
"He's a tough, tenacious young man," Rivera said. "He wants to get on the football field and help this team in any way he can."
Smith hasn't missed a game since sitting out the 2010 finale because of a strained calf.