The Demons have also dropped youngster Luke Tapscott, who is now an emergency with forward Ricky Petterd and tall Jack Fitzpatrick.
Clark will be absent after he suffered concussion against the Western Bulldogs last round.
Melbourne’s leading goalkicker sustained the set-back after he flew for a mark and landed head first into the MCG turf.
Initially, Clark looked in serious trouble, but he remarkably got to his feet and lightly jogged to the interchange.
Football manager Josh Mahoney said the club did not want to risk the boom recruit.
“Mitch was desperate to play this week, but he has been unable to meet some of the requirements set by the medical department and as a consequence will miss this week’s game,” he told melbournefc.com.au.
Sylvia has not played this season, after he suffered a back injury in Melbourne’s final NAB Cup clash against Port Adelaide at AAMI Stadium in March.
He also served a one match club suspension last round, which was initially intended for round one. But, as he was injured, Sylvia served the penalty last round, when he was cleared to play.
The midfielder/forward received the club suspension following an off-field incident in the lead-up to representing Australia in last year’s International Rules series. He was then left out of the Australian squad.
Grimes returns from a one-match suspension, after he engaged in rough conduct against Richmond’s Daniel Jackson in round three.
Tapscott has had a tough start to the season, after his pre-season was interrupted by a hip injury.
Meanwhile, tenacious defender/midfielder Clint Bartram will play his 100th AFL match this round.
The 24 year-old made his debut for Melbourne in round one, 2006.
Teams
Melbourne
B: James Frawley, Jared Rivers, Clint Bartram
HB: Cale Morton, Colin Garland, Jack Grimes
C: Jordie McKenzie, Brent Moloney, Tom McDonald
HF: Nathan Jones, James Sellar, Jeremy Howe
F: Colin Sylvia, Lynden Dunn, Aaron Davey
Foll: Mark Jamar, James Magner, Jack Trengove
I/C: Matthew Bate, Jack Watts, Rohan Bail, Joel Macdonald
Emg: Ricky Petterd, Luke Tapscott, Jack Fitzpatrick
In: Colin Sylvia, Jack Grimes
Out: Luke Tapscott, Mitchell Clark (Neck)
Milestones: Clint Bartram - 100 games
St Kilda
B: Jarryn Geary, Sam Gilbert, Jason Blake
HB: Tom Simpkin, Sam Fisher, Sean Dempster
C: Nick Dal Santo, Lenny Hayes, Brendon Goddard
HF: Jack Steven, Nick Riewoldt, Leigh Montagna
F: Stephen Milne, Rhys Stanley, Terry Milera
Foll: Ben McEvoy, Dean Polo, Clinton Jones
I/C: Jason Gram, David Armitage, Jamie Cripps, Jack Newnes
Emg: Tom Ledger, Arryn Siposs, Beau Wilkes
In: Jason Gram
Out: Justin Koschitzke (Suspension)
