The first-ever Canadian player to feature in Serie A suffered a broken tibia at practice on Tuesday, which will require surgery.
If he cannot play against Venezuela, manager Jesse Marsch may use Richie Laryea as an inverted wingback or bring Ali Ahmed into the fold.
Maxime Crepeau has staked his claim as the first-choice goalkeeper for this team over Dayne St. Clair, posting three clean sheets in his last four international appearances between the sticks.
Captain Alphonso Davies reached another milestone on matchday three, with the Bayern Munich wingback collecting his 50th cap for the national team.
Jonathan Osorio picked up his 75th cap for the Canucks on matchday three, playing in a holding midfield role alongside vice-captain Stephen Eustaquio.
Ismael Kone, who officially joined Marseille in Ligue 1 last week, should be back in the starting 11 on Friday after Marsch kept him out of the lineup against Chile because he was on a yellow card.
Coming on as a substitute on matchdays two and three, Tani Oluwaseyi has provided some energy off the bench, with the Minnesota United striker having his first international goal chalked off against Chile for offside.
Jonathan David is the only Canadian to score at this tournament, with the Lille striker now at 27 all-time, two fewer than Cyle Larin for the most in the history of this program.
Canada possible starting lineup: Crepeau; Johnston, Bombito, Cornelius, Davies; Kone, Eustaquio; Ahmed, David, Laryea; Larin