The Sydney AFL derby will be played in Ballarat with GWS and the Swans facing an extended stay in Victoria due to NSW's coronavirus crisis.
The two Sydney clubs might have to remain based in Melbourne for the remainder of the season with NSW's COVID-19 outbreak continuing to worsen.
The state recorded 112 new COVID-19 cases on Monday, with the NRL on Sunday following the AFL's lead and relocating its NSW teams interstate.
The AFL confirmed the GWS and the Swans game would go ahead at 1.45pm at Mars Stadium this Saturday - the last round-18 fixture to be finalised.
"The COVID-19 situation in NSW and associated border restrictions has meant we are unable to play the match in NSW," AFL clubs and broadcasting manager Travis Auld said.
"The upside of the unfortunate situation in NSW is that we can take what is a quality match-up to regional Victoria, with Mars Stadium in Ballarat once again being a great venue to accommodate the two clubs."
The Giants were hoping the game could be played in Canberra, having made Manuka Oval a second home base since the club entered the AFL in 2012, but that was ruled out when the Victorian government declared the ACT a red zone on Sunday.
GWS got a taste of Ballarat's Mars Stadium on Sunday, but lost to Gold Coast by a point.
The Giants upset the Swans at the SCG earlier in the season, coming from behind to win by two points.
Both clubs have been based in Victoria since June 22 and are pushing for family members to be able to join players and staff in Melbourne, but that still appears unlikely.
Star Giants midfielder Lachie Whitfield will miss the match after being diagnosed with a delayed concussion.
Whitfield was subbed out of Sunday's one-point loss to Gold Coast in the second quarter after experiencing a migraine following a hit to the head.
"Lachie obviously got a knock and he's had some migraine-type symptoms over the course of the last couple of years and that has led to some visual disturbances for him and that's what happened to him during the game," Giants head of medical Cullan Ball said.
"Unfortunately for Lachie, his symptoms deteriorated as the quarter wore on and ultimately he was ruled due to those visual disturbances.
"At that point, he was sent to hospital for observation and some further investigations to ensure he didn't have a facial fracture. Thankfully those investigations came back clear.
"He checked in with the medical staff again today and had his concussion assessment, which he failed, so he's now been classified as a concussion and will enter the return-to-play protocols and we'll see how he progresses over the next couple of weeks."