Hayes had missed three weeks because of the calf injury and he was substituted out of last Saturday's loss to the Bulldogs with what was initially believed to be a cork.
The three-time All Australian ran laps away from teammates at Thursday's main training session and coach Scott Watters confirmed he would miss Sunday's twilight clash against North Melbourne.
The Saints have their mid-season bye in round 12, meaning Hayes could be sidelined until the round 13 match against Melbourne.
"Lenny's probably a two to three week spell on the sidelines," Watters said on Thursday.
"We've got to be very cautious now with Lenny coming back.
"We'll weigh that up but he won't be available this week."
Key midfielder David Armitage is expected to return from a calf injury this week, and Watters suggested there could be more changes, with young midfielders Tom Ledger, Josh Saunders and Brodie Murdoch all in the mix.
Watters said the young trio's form warranted attention, but he was also mindful of balancing the workloads of his less experienced players.
"Saunders and Murdoch, if we play them every week they'll be cooked by about round 12," he said.
"I still want some of those younger players pushing up in rounds 18, 19 and 20.
"We're also very careful about managing our young players over the course of the year."
St Kilda has slipped to 2-7 but Watters highlighted the team had suffered four losses by less than 20 points.
While playing finals this season is all but out of reach, Watters said the pressure would still be on his players every week.
"We're hungry to get better … we're not comfortable where we sit," he said.
"We don't want to be at this stage of the season and have won two games.
"If you watch our young guys train and our older guys train, you wouldn't think that the pressure's off. They're working pretty hard."
Leigh Montagna will play his 200th game on Saturday and Watters paid tribute to the dual All Australian, who remains a key part of the Saints' midfield.
"He's been a good player in big games, he's a good player right now when we need our leaders to really stand up and lead, and I think he's been an outstanding contributor to this football club," the coach said.
"He's the sort of player that could play for another three to four years.
"It's a tribute to him and I hope we certainly support that performance this week."
Nathan Schmook is a reporter for AFL Media. Follow him on Twitter: @AFL_Nathan