The Flames announced Friday that Sean Monahan and Kris Versteeg will miss the remainder of the season due to injury.
"Sean has been battling through two injuries over the past month and it has reached a stage where it must be addressed," said GM Brad Treliving.
The Flames top-line centre, who has a team-leading 31 goals, will undergo surgery in the coming days.
Left-winger Versteeg had recently returned to the lineup after being sidelined 48 games due to hip surgery.
Defenceman T.J. Brodie and left-winger Matthew Tkachuk did not travel with the team for their two-game road swing through California, that begins with a Saturday matinee against the San Jose Sharks.
"Brodes, both him and Chucky are still day-to-day," said coach Glen Gulutzan. "We're still hoping that at some point they can come back."
2017-18 INJURY LIST
Total regular-season man-games lost - 137
March 23 - Out for Season: Sean Monahan
March 21 - Out for Season: Kris Versteeg (lower body) - 1 game
March 19 - Present: TJ Brodie (upper body) - 2 games
March 13 - Present: Matthew Tkachuk (upper body) - 5 games
Feb. 17 - Present: Marek Hrivik (upper body) - 19 games
Feb. 24 - March 5: Michael Ferland (upper body) - 5 games
Feb. 13 - March 11 - Mike Smith (lower body) - 13 games
Feb. 9 - Feb.19: Troy Brouwer (upper body) - 6 games
Jan. 4 - Jan. 29: Jaromir Jagr (undisclosed) - 10 games
Jan. 14 - Sean Monahan (illness) - 1 game
Dec. 31- Jan.30: Michael Frolik (upper body) - 12 games
Dec. 22-Dec. 27: Travis Hamonic (lower body) 1 game
Dec. 20- Dec. 27: Jaromir Jagr (lower body) - 2 games
Nov. 28-Dec. 15: Jaromir Jagr (lower body) - 6 games
Nov. 25 - March 16: Kris Versteeg (lower body) - 49 games
Nov. 13: Mike Smith (upper body) - 1 game
Nov. 5 - Nov. 9: Travis Hamonic (lower body) - 3 games
Oct. 22 - Nov. 7: Jaromir Jagr (lower body) - 6 games
Oct. 13 - Oct. 18: Micheal Ferland (lower body) - 1 game
Oct. 4 - Oct. 11: Marek Hrivik (upper body) - 4 games