The fourth annual "Spud's Game" will be staged at the MCG for the first time, when St Kilda take on premiers Collingwood in round two on a Thursday night.
It is a fundraiser for the Danny Frawley Centre, which was established at the Saints' Moorabbin headquarters as a lasting tribute to the club great nicknamed Spud.
Frawley died suddenly five years ago and the centre, plus its in-house charity, aim to foster mental health in the community.
As if the Frawley family has not dealt with brain health enough, last week Melbourne star Angus Brayshaw retired because of concussion issues.
His fiance is Danielle Frawley, Chelsea's younger sister.
But for all the seriousness around Tuesday's announcement of the round-two game, the thought of "Spud" Frawley's reaction to such an honour prompted plenty of smiles.
As well as captaining St Kilda and coaching Richmond, Frawley was also an assistant at the Magpies.
"I don't think his head (could have gotten) any bigger, but it probably would explode," Chelsea said with a chuckle.
"Thursday night against Collingwood, he would be so ecstatic.
"I know he absolutely loved his time at the 'Pies."
Frawley's death has become a tragic, but significant, milestone in how mental health and concussion issues are dealt with in the AFL.
On Monday, Melbourne captain Max Gawn noted Brayshaw had received proper support from the league and the club in dealing with his concussion issues.
"As a family, we're so thankful to the Saints for giving us the platform of Spud's Game, to promote what we're doing here at the centre," said Chelsea, who is heavily involved at the centre.
"Five years ago, some of the testing that's out, wouldn't (have been) here.
"Although it took a few lives to be lost, to actually get to the point now where we're focusing on the importance of protecting the brain and how sacrosanct the brain is, it's really positive."
Collingwood forward Dan McStay missed their grand-final win because of a knee injury and then he needed a knee reconstruction after a November training injury.
He is grateful for the support around him as he dealt with those major setbacks.
"Definitely my mental health, probably the last six months have been pretty hard - I've had to battle through a fair bit," he said.
As well as confirming the round-two game, the Saints on Tuesday also announced a partnership with the Institute of Social Neuroscience, who will set up a clinic at the Frawley Centre.
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