Head coach Adam Foote says the star defencemen is “day-to-day” with a lower-body injury.
Hughes logged 26 minutes and 25 seconds of ice time and registered two assists in Vancouver’s 4-3 loss to the Montreal Canadiens on Saturday.
He has one goal and six assists over nine appearances for the Canucks (4-5-0) this season.
The 26-year-old American blue liner was plagued by injuries last season, including a torn ligament in his hand and an oblique tear.
Hughes still managed to register 16 goals and 60 assists across 68 regular-season games, but missed playing for the United States in the 4 Nations Face-Off tournament.
Victor Mancini will slot into the lineup as the Canucks’ sixth defenceman.
— With files from Sportsnet Staff