Saturday's history-making Super Rugby fixture in Ballarat could set the tone for the Melbourne Rebels' season.
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The club will take on the Sharks, which hold third spot in the South African conference.
Rebels captain Dane Haylett-Petty said a win in Ballarat would mark the first in two years against the South African-based club.
"Because we play local teams more often, these wins are like double points," he said.
"These are the ones that really matter, because they differentiate you from teams in your pool."
Saturday's match will mark the first professional rugby match in the city in over 20 years. It will also mark the first ever Super Rugby regular-season contest held outside a major city.
"It's the first time in Australian history Super Rugby has gone regional," Haylett-Petty said.
"We've got two teams that like to attack. There are world-class rugby players on both sides, so it should be a great game and entertaining for the fans."
The match, beginning a 2.30pm, will follow a Super-W clash between the Melbourne Rebels and Canberra-based Brumbies.
Melbourne will be looking for its first win of the Super-W season, following last Friday's 33-3 loss at home to the Waratahs. The match will begin at 12:15pm.