MacKinnon was hurt after taking a hit in the corner from Canucks defenceman Alexander Edler with about six minutes left in the second period.
The 22-year-old, whose helmet popped off as a result of the collision, skated slowly to the Colorado bench and appeared to be favouring his left shoulder.
MacKinnon was briefly attended to by a trainer before heading to the locker-room.
"I really don’t know a timeline. It’s upper-body," said Avalanche head coach Jared Bednar. "I don’t know if it’s day-to-day or not. I’ll have to talk to the trainers. We’ll probably know more (Wednesday)."
MacKinnon, who assisted on the Avalanche’s first goal against Vancouver, has 61 points on the season (24 goals, 37 assists) to sit three back of Tampa Bay Lightning winger Nikita Kucherov for the NHL lead.
Colorado, which has now dropped three straight after winning 10 in a row, visits Edmonton on Thursday.