St Kilda defender Logan Austin will undertake surgery later this week on his injured left shoulder.
Austin is expected to miss a significant period, however, an exact time frame for his return has not been set.
"It's a frustrating outcome for Logan after doing a lot of work to get himself fit after a groin issue in the pre-season," St Kilda football manager Simon Lethlean told AFL Media.
"But surgery is the best option to repair the damage to the joint and ultimately set him up for the rest of his career."
Promising St Kilda defender Oscar Clavarino has also been ruled out for up to three weeks, as he recovers from an ankle sprain.
Forward Matthew Parker is in doubt to play against Melbourne, after battling an ankle injury.
Parker hurt himself in the second quarter of Sunday's game against Hawthorn, however ended up finishing the match on the field.