Each sustained a lower-body injury in the second period of a 4-3 overtime loss to the Ottawa Senators on Thursday.
MacKinnon's last shift came with 8:15 remaining in the second. The forward grabbed his right side after attempting a reverse hit on Senators defenseman Artem Zub and stayed on the bench for a few minutes before heading down the tunnel.
Makar took a shift at 10:44 of the second period that lasted only four seconds before heading to the locker room. He briefly returned for a 23-second shift that ended with 5:20 remaining, but stayed on the bench for the rest of the period. The injury came four days after he left practice on Sunday for precautionary reasons.
"When I think about those two guys, it's like every matchup, they take it on, now someone else has to be able to step up and do that," Avalanche coach Jared Bednar said Saturday. "And then you are losing the depth down the lineup as you kind of do that because everyone is elevated."
Colorado will play its first game without the two against the Montreal Canadiens on Saturday (7 p.m. ET; (7 p.m. ET; TVAS, SNE, ALT2, KTVD).
MacKinnon leads the Avalanche and is fifth in the NHL with 30 points (10 goals, 20 assists) in 20 games; Makar is third on Colorado and tied for third among NHL defensemen with 23 points (five goals, 18 assists) in 19 games.
MacKinnon was a Hart Trophy finalist last season when he led the NHL in goals with 53 and was third with 127 points (74 assists). He led the NHL with a plus-57 rating.
The No. 1 pick by Colorado in the 2013 NHL Draft, MacKinnon has 1,172 points (430 goals, 742 assists) in 970 regular-season games and 140 points (62 goals, 78 assists) in 108 Stanley Cup Playoff games. He had 24 points (13 goals, 11 assists) in 20 playoff games to help Colorado win the Stanley Cup in 2022.
MacKinnon has had at least 100 points in each of the past four seasons. Since entering the NHL in the 2013-14 season, he is second in points, third in assists and fourth in goals. He won the Calder Trophy as the top rookie in 2013-14, and the Hart Trophy and Ted Lindsay Award (MVP as voted by the NHL Players' Association) in 2023-24.
"It's a big task but we are all excited for it," forward Martin Necas said. "It is what it is. We still have good enough players that we can kind of figure (it) out."
Makar, the No. 4 pick by Colorado in the 2017 NHL Draft, has 530 points (141 goals, 389 assists) in 489 regular-season games and 90 points (26 goals, 64 assists) in 90 playoff games. That included 29 points (eight goals, 21 assists) in 20 games in 2022 when he won the Conn Smythe Trophy and Colorado won the Stanley Cup.
Makar has won the Norris Trophy as the NHL's best defenseman twice (2021-22, 2024-25) and has been a finalist each of the past six seasons. He also won the Calder Trophy in 2019-20.
"I'm sure it's going to be a big challenge, a big test for our group," forward Artturi Lehkonen said Saturday. "Missing two of the best players in the world, you can't really replace that. ... They are a huge part of our offense. Got to find different ways to create offense and score goals today for sure."
NHL.com independent correspondent Sean Farrell contributed to this report
