Mayo by-election candidate Rebekha Sharkie says she is "nervous but hopeful" that she will be re-elected to the South Australian seat, following a campaign where she has sought to leverage her local knowledge against her main opponent, Liberal newcomer Georgina Downer.

"We've given this everything that we can possibly give it, so look, you can only be hopeful and you can only be optimistic," Ms Sharkie said.

"I love my community, that is why I put my hand up two years ago, that is why I put a second mortgage on our house two years ago."

Ms Sharkie was in Mount Torrens on Saturday morning, deep in friendly voter territory close to her family home.

Before she placed her vote at the Spring Head Lutheran School polling booth, Ms Sharkie pointed to negative attacks in the hotly contested campaign for Mayo and her party Centre Alliance's support for truth in political advertising laws.

"If you get distracted by that, you lose your own message and your own mission," she said.

Rebekha Sharkie voted at the Mount Torrens. ( ABC News: Isabel Dayman )

"There is no doubt that I have been up against a million-dollar campaign and I don't have those resources and I knew I wasn't going to do it, so we had to be clever and resourceful with what we had."

Ms Downer spent her morning at the polling booth in the leafy green Adelaide Hills suburb of Stirling, close to her childhood family home where she grew up with her father, the former member for Mayo and foreign minister Alexander Downer.

Liberal candidate for Mayo Georgina Downer voted at the Stirling polling booth. ( ABC News: Isabel Dayman )

Ms Downer said that people in Mayo were concerned about cost of living and job creation and highlighted her family's history in the area.

"This is an electorate that I have grown up in, this is an electorate that my family has been in for over 100 years," Ms Downer said.

"I've always thought I was the underdog — I'm up against an incumbent and that's always a challenge and of course historically governments don't win these by-elections off the Opposition.

"It's going to be a challenge, I do think I'm the underdog but we have run a fantastic campaign here supported by hundreds and hundreds of volunteers."

She confirmed she would run as the Liberal candidate for Mayo in the 2019 federal election, regardless of the by-election result.

"That's my absolute commitment — I'll be running next year," she said.

Ahead of the opening of the polls, Prime Minister Malcolm Turnbull leant his support to Ms Downer to return as the Liberal candidate for Mayo for the federal election next year, no matter the outcome at the Saturday by-election.

He told The Advertiser Ms Downer was an "outstanding candidate" for the party, with the federal election to be held in the first half of 2019.

Ms Downer has previously said that while she was running to win the Mayo by-election, she intended to put her hand up for preselection to run in the next federal election and was committed to Mayo for "the long haul".

Liberals keen to snatch back Mayo

Sorry, this video has expired Here's why Antony Green thinks you should pay attention to the by-elections

The hotly contested seat has seen a conga line of senior Liberal figures flown in to lend support to Ms Downer's campaign, as the Liberals attempt to wrest back the normally blue-ribbon seat from Ms Sharkie.

Ms Sharkie was elected to the seat in the 2016 election, with the sitting MP Jamie Briggs losing the safe Liberal seat in a massive swing following local backlash over an incident in Hong Kong involving Mr Briggs and a female public servant.

But despite the Liberals efforts, successive polls of the electorate have placed Ms Sharkie as the favourite, with Ms Downer battling a local groundswell of the "blow in" factor, combined with resentment about perceptions of family entitlement.