The state executive of the ALP is expected to open nominations on Friday to find Mr Weatherill's replacement in the safe Labor seat.

Announcing his resignation to the parliament, Mr Weatherill said it had been a privilege to serve over his 16-year political career, and paid special tribute to his family.

"I don't know how, frankly, you can be sustained in a leadership role in politics without the love and affection of a family," he said on Thursday.

He also cited the difficulties posed for political parties when former leaders linger.

"Obviously I've got points of view but if I share them, even with the caucus, it creates attention," he said.

"It's time for me, having run my race, to hand the baton on."

His departure is likely to clear the way for a by-election early in the new year, with Labor's candidate for the widely tipped to be Unions SA secretary Joe Szakacs.

But opposition leader Peter Malinauskas said he expected a number of quality candidates to nominate.

"I think there's a large number of people that are likely to be interested in an opportunity like this," he said.

"What's important is that we get the right result."

Australian Associated Press