Ryan O'Reilly scored Colorado, which has lost three straight.
The Avalanche have cooled off after setting a franchise record for the hottest start through 16 games. They dropped road games in Carolina and St. Louis and came home looking to turn things around against lowly Florida.
Instead, the Panthers, who played Friday, looked like the fresher team throughout. They outshot Colorado 14-10 in the first period and had more scoring opportunities. They cashed in when Scottie Upshall found Boyes alone in front of the net, and he beat Colorado goalie Semyon Varlamov with a wrister to make it 1-0 with 7:20 left in the first period.
Varlamov finished with 29 saves.
Colorado stayed on its heels in part because of four penalties — one a double-minor for high sticking by Nate Guenin. The Panthers capitalized on that early in the second when Campbell's slap shot from the top of the circle beat Varlamov to make it 2-0 1:15 into the frame.
The Avalanche cut the deficit in half when O'Reilly's shot went off Gilbert's leg and past Thomas early in the second, but Kopecky restored the two-goal lead when he scored 2 seconds after Colorado killed off its fifth penalty in the first 33 minutes of the game.
Colorado amped up the pressure in the third, but couldn't get one past Thomas, who made 15 saves in the period. Huberdeau sealed it with his fifth goal at 12:16 of the third.
NOTES: Upshall had two assists. ... Avalanche D Matt Hunwick was in the lineup for the first time since being recalled from Lake Erie of the AHL on Nov. 4. ... The Panthers are in the midst of a five-game, eight-day Western Conference road swing. Colorado is their second stop. ... Avalanche LW Cody McLeod's wife Jessica gave birth to a baby girl early Saturday morning. ... Florida's five wins have come against teams with winning records.