Webster is set to undergo surgery after breaking his hand in the Saints' win over Fremantle on Sunday, with the club hopeful he should have a "speedy recovery".
Bytel meanwhile will miss Round 2's clash against the Western Bulldogs after being admitted to hospital with a cut knee, where he got the wound cleaned out.
St Kilda's acting General Manager of Football, David Misson, said it was disappointing to lose the duo, but revealed that Marcus Windhager will be available for selection after recovering from a broken hand.
“Jimmy is such a courageous player and it's disappointing for him to hit a roadblock like this,” Misson said.
“The injury is comparable to Marcus', so we're hopeful for a similarly speedy recovery for Jimmy.
“Jack suffered a cut to his knee early in the game which was attended to and he returned to the field. However, his discomfort continued post-match and Jack was admitted to hospital later that evening.
“Jack then underwent a clean-out of the wound, resulting in disruption to his preparation this week.
“Marcus was very close to playing last week, but didn't complete the necessary training load for him to be selected. As has been a constant with Marcus, he's put his head down during rehab and we're pleased to have him available for Round 2.”
Misson also confirmed that Tim Membrey's return doesn't have a "definite" date, with the key forward suffering setbacks in his recovery from a knee injury.
St Kilda next face the Bulldogs on Saturday night at Marvel Stadium, hoping to win their second match from as many games.