Star midfielder Sam Walsh and dynamic forward Jack Martin could join vice-captain Jacob Weitering on the sidelines for Carlton's opening round clash with the Brisbane Lions.
Walsh experienced back soreness last week and has already been ruled out of the Blues' only two practice matches.
It is a major blow for Carlton, who will already be without star defender Weitering for a rematch of last year's preliminary final at the Gabba on March 8.
Walsh, who who won the Gary Ayres Medal as the best player of last year's finals series, missed the first four games of last season after having surgery to fix a bulging disc in his back.
The 23-year-old later admitted it took him a long time to return to his best following the invasive procedure.
Walsh's form resurgence coincided with Carlton's extraordinary end to 2023 as the Blues made the finals for the first time in 10 years.
"Sam experienced back soreness after completing match simulation last Monday. After further assessment it has been decided to reduce his training loads," Carlton football boss Brad Lloyd said.
"We will take a no-risk approach with Sam's return to play, therefore he will not feature in the upcoming practice games, with the club to provide a further update on Sam's progress prior to our clash against Brisbane."
Martin, who was important in two of Carlton's three finals last year, suffered a MCL sprain in his knee and is listed to return in "two-to-three weeks".
Weitering is back in full training after injuring his calf but will miss at least the game against the Lions and the blockbuster clash with Richmond six days later.
Tall utility Jack Silvagni has begun the initial stages of his recovery after rupturing his ACL last month, but will miss the entire season.
Carlton will host Geelong in a practice match at Ikon Park on Thursday and will return to the same venue next Wednesday to face Melbourne in their final hit-out before playing Brisbane.
