MacKinnon, who sustained a leg injury during a 3-2 overtime loss to the Pittsburgh Penguins on Wednesday, did not take part in the morning skate.
Colorado will be looking to extend its season-opening point streak to seven games. The Avalanche won their first five games before losing against the Penguins. Colorado is the only team without a regulation loss.
The Panthers are home after going 1-0-2 on a three-game road trip. They ended a three-game losing streak when they rallied from down 4-1 for a 6-4 win against the New Jersey Devils at Prudential Center on Monday.