Hawthorn coach Alastair Clarkson said Mitchell is certain to miss the match after the star onballer lasted just 20 minutes before being subbed with a right hamstring injury.
Meanwhile, Lake looks doubtful after succumbing to a right calf injury during the third quarter.
Five talking points: Hawthorn v St Kilda
"I'm not really certain with 'Lakey'," Clarkson said following the demolition job on the Saints.
"It looked like he'd been shot and then he recovered really well once he got to the bench.
"He's got a niggle in the calf, what it is we’re just uncertain of at this point in time. So you'd reckon he'd be in doubt too. He was unable to come back onto the ground."
The Hawks smashed the Saints by a club-record 145 points, controlling every facet of the game on a wet afternoon at the MCG.
The reigning premiers dominated the possession count (478-329), marks (114-62) and inside 50s (68-25), and also won contested ball, hit-outs and clearances.
Thirteen Hawks had 23 possessions or more, including first-gamer Billy Hartung, who gathered 26 touches with six marks and kicked 1.1 in only three quarters of game time.
The thumping win was a fitting celebration for Jordan Lewis' 200th game and a near faultless performance.
"We don't judge it in that regard," Clarkson said post-match.
"We judge it in terms of the three elements of the game – when we've got it, when they've got it and when the ball is in dispute – and we were strong in all facets of the game today, so we were really pleased with that.
"But we know full well it's not going to be that easy next Friday night.
"It's not often that you turn up and get a day like that today, but we know that we've got Sydney next Friday night up at ANZ (Stadium) and that's going to be a tough assignment for us."
Even without Lake, the Hawks have the depth to match-up on Franklin in Josh Gibson, Ben Stratton and Ryan Schoenmakers.
Gibson held Nick Riewoldt goal-less on Saturday and collected 30 touches of his own, while Stratton (corked hip) could be in the frame to return after being a late withdrawal against the Saints.
Schoenmakers showed he has the ability to play back and forward – booting four goals in less than three quarters before being pushed back to cover for Lake in an impressive return from a knee reconstruction.
Clarkson will mull over the best fit for 'Buddy' this week – if Franklin recovers from a knee injury in time – but said the two-time premiership Hawk is now just "another opponent".
"We're not even sure if 'Buddy' will play, if he does it's just another guy we've got to come up against," he said.
"We know him pretty well, but they've got 21 others that we've got to worry about. He'll just be wearing a red and white jumper.
"They're a really good side, they've started the season a little bit slower, but they're starting to hit their straps a little bit now so we’re looking forward to that contest.
"It will be a great challenge for us and it will be on for young and old, I'm sure."
Hawthorn players carry Jordan Lewis from the ground after his 200th game (below). Picture: AFL Media