A big swing to Labor is threatening what was once a safe Liberal seat and giving the ALP a tantalising prospect of a majority government in South Australia.

The counting of votes continues from the Fisher by-election in Adelaide, and Labor's Nat Cook is leading Liberal Heidi Harris 52 to 48 per cent, two-party preferred.

High-profile independent candidate Dan Woodyatt also polled strongly and had the backing of the widow of Fisher's former independent MP Bob Such.

Dr Such was a Liberal before he quit the party in 2000.

The ALP last held the southern Adelaide seat about three decades ago.

If Labor does pull off an upset win in Fisher, it will let Premier Jay Weatherill's team govern in its own right after it formed a minority government back in March.

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Thousands of pre-poll votes remain to be counted in coming days.

ABC election analyst Antony Green said the chance of a Labor win seemed extraordinary.

"It is not very often that governments gain seats at by-elections," he said.

"The examples I can think of all took place during first terms of government, not the fourth term, which is the current position of the Weatherill Government in South Australia."

Mr Weatherill said the big swing to Labor showed voters' dissatisfaction with broken promises from the federal Coalition Government.

"Whatever else happens, this has been an extraordinary result," he said.

"I mean a fourth-term government with a by-election in a safe Liberal seat getting something in the order of about a 9 per cent swing to the Labor Party, this sends a clear and unmistakable message to Tony Abbott in Canberra: 'Break your promises at your peril.'"

Mr Weatherill said speculation that a new fleet of submarines would be built overseas instead of in Adelaide as originally promised played a role.

"The people of Fisher wanted somebody that's prepared to stand up for South Australia and fight for this promise to be kept - 12 new submarines built in South Australia," he said

"They looked at the Liberal Party likely and saw they weren't standing up for South Australia. [The state Liberals were] making excuses for Tony Abbott."

Federal Liberal MP Jamie Briggs said federal issues such as Senator Johnston's submarine comments had a "large impact" on the Fisher swing.

"David Johnston regrets making them, he's apologised, he was right to apologise for them. We all make mistakes in this business and unfortunately this mistake has cost us a significant amount of support at the wrong time for the campaign in Fisher," he said.

The manager of the Liberal campaign in Fisher, state MP Rob Lucas, said it was fortunate the federal Liberals were not facing the prospect of a by-election any time soon.

"Particularly in SA because the decisions that have been taken and the statements that were made about not being able to build canoes et cetera have created a very unfavourable environment for the whole Liberal brand in SA," he said.

'Pressure' on SA Liberal leader Steven Marshall

SA Liberal leader Steven Marshall agreed with the view that Senator Johnston's comments about defence builder ASC adversely affected the Fisher campaign.

But he said it was still too soon to speculate on how much it had affected the outcome.

"I've made it very clear that I think that the comments that were made by Senator Johnston were damaging and they were incorrect and they had an effect," he said.

"But we don't have a result yet so let's wait to see what that result is going to be before we apportion blame."

University of Adelaide politics analyst Clem Macintyre was among those who questioned how secure Mr Marshall's leadership might be.

"Certainly it's increased the pressure on Steven Marshall within the Liberal Party, to my mind there's no question about that," he said.

Hopes pinned on pre-poll votes: Liberal candidate Heidi Harris with party leader Steven Marshall (R). ( ABC News )

Another federal Liberal MP Rowan Ramsey was swift to defend the State Opposition Leader, saying Mr Marshall retained the full support of his party colleagues.

"I think Steven Marshall has the full confidence not only of the parliamentary team but of the lay party as well," he said.

"[He is] a young member of parliament, he's only on his second term, sure everyone is doing a bit of learning but he's learnt pretty fast.

"He's confident, he has a very good business background, he's wide and varied and a good rapport with people. I don't think there'll be any likelihood of any change."

SA federal Liberal MP, Andrew Southcott, said there was no doubt federal issues played a part in the party's performance in Fisher.

"Certainly the comments from the Defence Minister [about submarines] were used in the campaign, they appeared on posters within a few days, so they were certainly promoted by the Labor Party," he said.

Liberal candidate Heidi Harris remained hopeful of sitting in the Parliament after the Christmas break.

"We hope to pick up a lot of votes at the early voting centre so we'll just have to wait and see," she said.

South Australia's Liberals will face another electoral test next month in the Adelaide Hills seat of Davenport, where former state Liberal leader Iain Evans retired recently.

At the time he had hoped to force two state by-elections on the same day, but the Davenport poll was later set for January 31.

At the state election last March, the Liberals held Davenport with a margin of just over 8 per cent.