After key defender Ben Stratton injured his knee in the win over Richmond in round four and was ruled out for the season, Alastair Clarkson's men could ill-afford to lose another key defender.
But in the opening three minutes of the St Kilda match Stephen Gilham went down with a serious right knee injury.
He will have scans on Monday, but the Hawks fear the worst.
It will be now be left to the under-sized Josh Gibson and Luke Hodge to fill the void left by Gilham, who was described by Clarkson as the 'stalwart' of the Hawks defence.
The day got worse when David Hale landed awkwardly after spoiling Saints ruckman Ben McEvoy in a marking contest midway through the second quarter.
After trying to find his feet, Hale was stretchered off the ground with the trainer cradling his right knee. He finished the match with his right knee heavily bandaged and on crutches.
Hawthorn supporters will hope for good news concerning the ruckman, but with number one big man Brent Renouf still on the sidelines with a hamstring injury, they may have to turn to forward Jarryd Roughead to take up the reins, as he did against the St Kilda duo of Justin Koschitzke and McEvoy.
Clarkson said the performance of Roughead in the ruck epitomised the Hawks' resolve and strength of character after they found themselves 33 points down early in the second quarter and reduced to just two on the bench.
"I don't think anyone anticipated that with Renouf and Hale injured, he would have to shoulder the bulk of the responsibility [in the ruck]," he said.
"It was such a lion-hearted effort today to not only get in there and compete, but we won the clearances convincingly as well."The brave performance of Roughead was one of many in the Hawks' stirring win.
Hodge, who made a slow start to the season following his battle with Achilles issues, is beginning to have greater impact, to the delight of his coach, who described his performance against the Saints as his best game of season 2011.
"I thought 'Hodgey's' leadership through the middle… he has taken a while to get going, but his contribution today was very important for us," he said.
With Cyril Rioli set to be back next week and Cameron Bruce inching closer to a return, the Hawks can hope to build on their back-to-back wins with clashes against the Sydney Swans, the Western Bulldogs and Fremantle to follow.
The serious injuries offer a challenge to Clarkson and his men, but after their performance against St Kilda and the continual improvement of the youngsters such as Shane Savage and Paul Puopolo, the injuries provide a chance for a young Hawk.
"As tough as it is and as disappointed as we are in losing some players, it just the simple case of one door closes and another one opens and an opportunity for a young bloke," Clarkson said.
"It's a ruthless game, we just have to move on as quickly as we can."
