Nasiah Wanganeen-Milera will be sidelined for three weeks in a significant blow for St Kilda.
The Saints star was a late withdrawal from Saturday night's loss to Gold Coast in Darwin.
He was managed because of a knock to his lower leg in the previous game against Carlton.
Scans have shown the star on-baller has a calf strain. It means he will miss this Sunday's game against Richmond, then key clashes against Fremantle and Hawthorn.
"We gave Nas every opportunity to get up for Saturday night, but ultimately decided to err on the side of caution," Saints football boss Lenny Hayes told the club website.
"Despite presenting with minimal pain, results from his latest scan have confirmed a minor strain."
Co-captain Cal Wilkie will need to pass a fitness to play against the Tigers, meaning his 164- consecutive games streak might continue.
Wilkie, who has not missed a game since his debut, was forced off the ground when Suns forward Ben King kneed him in the back in a marking contest.
Hayes said a scan had cleared Wilkie of internal damage.
Jack Higgins could resume from concussion, but Liam Ryan is also out of action for three weeks with a calf injury.