The Sharks (43-20-8) are one point ahead of the Calgary Flames for first place in the Pacific Division. They would have become the first Western Conference team to clinch a berth in the Stanley Cup Playoffs with a victory.
"Sure, every time you lose a game it's opportunity lost, but you're not going to win every game the rest of the way," San Jose coach Peter DeBoer said. "Two weeks ago, we were seven points back. I think we're in a pretty good spot, and we worked awful hard to get there."
WATCH: [All Panthers vs. Sharks highlights]
The Panthers (31-27-12) are seven points behind the Columbus Blue Jackets for the second wild card into the playoffs from the Eastern Conference.
"We're not out of it yet," Florida coach Bob Boughner said. "We know it's a long way to get there, but we're concentrating on winning every game. That's the goal. ... We're not giving up till the end. We're going to fight."
Jamie McGinn, Dryden Hunt, Mike Hoffman and Frank Vatrano scored for Florida, which won its third straight game and is 4-1-0 in its past five against San Jose. Rookie Sam Montembeault made 26 saves to win his third straight start overall and his first NHL start on the road.
"I was just doing what worked for me before, focusing on my game and wasn't getting intimidated by the crowd," Montembeault said.