Zak Jones has joined St Kilda's lengthy list of round one absences after failing to prove his fitness in time for their opening round clash with GWS.
Jones had looked on track to recover from a pre-season hamstring injury in time to face the Giants on Sunday but coach Brett Ratten ruled the midfielder out on Friday.
St Kilda were already without Max King (concussion), Brad Crouch (suspension), Dan Hannebery (calf), James Frawley (hamstring), Jarryn Geary (leg), Rowan Marshall (foot), Paddy Ryder (personal leave) and Ben Paton (leg) against the Giants.
"Zak hasn't done enough, he won't play this week," Ratten said.
"He was close - he just missed out on a little bit of running during the week, he got a little bit of a corky that set him back a little bit.
"We think with some of the injuries we've got, we don't need to take another risk.
"It's a long year, he's a quality player and very valuable, so we need to take fit men into round one and we're going to do that."
Ratten admitted he was still getting his head around the idea of King missing the game after suffering a concussion from being hit in the head by a golf ball.
"I was on the phone to the doc and I was waiting for the Benny Hill music to come over the top. It was unbelievable," Ratten said.
"I did say to Max the other day he'd be able to write a little chapter in his book about round one, 2021 - where he missed the game and how it happened."
Dynamic midfielder Jade Gresham will line up against the Giants after missing a large chunk of 2020 with a back stress fracture.
Intercepting defender Tom Highmore, 22, and mature-aged ruck recruit Paul Hunter will both make their AFL debuts.