Gold Coast defender Rory Thompson will make his AFL comeback after almost four years out of action, while rival captains Marcus Bontempelli and Joel Selwood have been sidelined by injuries.
Western Bulldogs skipper Bontempelli (foot/ankle) will miss his side's crunch clash with Port Adelaide and Selwood (corked quad) is out of Geelong's meeting with GWS.
Fellow superstar Dustin Martin's return for Richmond after six weeks away on personal leave sets up a blockbuster clash with Collingwood.
Thompson, who last played at senior level in July 2018, will return to the Suns' back-line against Sydney at the SCG on Saturday.
It will be his first AFL appearance in 1379 days.
During that time, Thompson ruptured the anterior cruciate ligament in his left knee and then partially tore the same ligament in his right knee.
The 31-year-old has impressed in three VFL matches this year to earn his recall.
"It's been a lot of hard work and thanks to everyone who has helped out along the way," Thompson said.
"It's been a bit of a tough journey but all of the players and staff have made it so enjoyable and I've still loved coming in every day through it all.
"I can't wait to pull on the Suns guernsey and run out with the boys again."
Gold Coast will take on a Sydney side bolstered by the immediate return of Paddy McCartin and Logan McDonald after one week out through concussion protocols.
COVID-19 issues have wreaked havoc with both Western Australian clubs.
Luckless West Coast have again been decimated by COVID-19, losing coach Adam Simpson and a host of players to health and safety protocols.
The Eagles also have a long injury list and have been left with just 22 AFL-listed players available for their clash with Brisbane.
Both sides were given an extension until Friday to lodge their teams.
Cross-town rivals Fremantle have limited the damage to six players out of their clash with North Melbourne through health and safety protocols, including key talls Griffin Logue, Rory Lobb and Lloyd Meek.
But ruckman Sean Darcy returns from concussion and young key forward Jye Amiss will debut.
The Kangaroos have recalled Ben McKay and Jed Anderson for Friday night's clash at Optus Stadium.
Anderson has played several games at VFL level after undergoing a training block to make up for his time away when he did not comply with the AFL's vaccine mandate.
As well as Bontempelli, the Bulldogs have lost Mitch Wallis (foot) for their trip to Adelaide Oval on Friday night, while Port Adelaide go in unchanged.
Selwood's absence for Geelong is offset by Patrick Dangerfield's return from a calf injury and Cooper Stephens, the Cats' top pick in the 2019 draft, will make his long-awaited debut against GWS, who go into Saturday's clash in Canberra unchanged.
Essendon midfielder Dylan Shiel returns to the starting 22 against Hawthorn after being dropped to the substitute role last week but Jake Stringer (hamstring) and Nik Cox (ankle) are key outs.
The Hawks have recalled Josh Ward and Denver Grainger-Barras.
Rowan Marshall and Zak Jones are high-profile inclusions for St Kilda as they try to end Melbourne's unbeaten streak on Sunday, while Adelaide dropped experienced midfielder Matt Crouch for their meeting with Carlton.