Gwilt missed last Friday night's loss to Richmond with a knee injury and will be sidelined for between three and five weeks, robbing the Saints of their best lockdown tall defender.
Dempster, meanwhile, broke his wrist midway through the second quarter against the Tigers and will miss three weeks after playing out the match.
The Saints' backline was stretched in round two, with star Richmond forward Jack Riewoldt kicking seven goals opposed to Jason Blake and later Sam Fisher.
It was Fisher's first match for the season after a foot injury sidelined him for the round one loss to Gold Coast at Metricon Stadium.
The Saints take on Greater Western Sydney at Manuka Oval on Saturday before clashes against Essendon (Etihad Stadium), the Sydney Swans (New Zealand) and Collingwood (Etihad Stadium).
Dempster was the Saints' best-performed defender in 2012, earning All Australian selection, and his wrist setback is a cruel blow having just returned from a hamstring injury.
Watters stressed post-match that the Saints only sent Dempster back onto the ground after the team's medical staff declared him fit.
"I don't want to get too caught up in the specifics other than he had broken a bone in his wrist," Watters said.
"He was still cleared, obviously. We wouldn't put a player back out there if he wasn't cleared from our doctor.
"There are minor fractures and severe fractures. It was taped and he was okay to play in the role that we had him in.
"Again we needed him out there, (but) there was no way that we would have a player out there if there was any potential long-term ramifications, so again we rely heavily on our doctor."
Rhys Stanley played forward against Richmond before moving back in the last quarter as a loose man. It is likely the Saints will use him as a defender while covering the injuries to Gwilt and Dempster.
Nathan Schmook is a reporter for AFL Media. Follow him on Twitter: @AFL_Nathan
