The president is scheduled to be Jakarta on Thursday. Mahfud did not say why he would be stepping down from the job.
Coordinating Minister for Political, Legal and Security Affairs and vice presidential candidate Mahfud MD on Wednesday said that he would tender his resignation to President Joko "Jokowi" Widodo once he has the chance to meet the president.
The president is scheduled to be Jakarta on Thursday. Mahfud did not say why he would be stepping down from the job.
Mahfud is the running mate of former provincial governor Ganjar Pranowo, who is up against Defence Minister Prabowo Subianto, and ex-Jakarta governor Anies Baswedan.
"I will say my goodbye to the president with honour. I will report to him that I am done (with the job)," Mahfud said in a statement live-streamed on his Instagram account.
The office of the president did not immediately respond for request to a comment.
Indonesia is to have its presidential and legislative election on Feb. 14.
Mahfud's resignation comes amid speculation and reports in local media about the potential resignation of respected Finance Minister Sri Mulyani Indrawati.
The finance ministry has said Sri Mulyani is continuing to carry out her duties in managing state finances.
Opinion surveys show the pairing of Ganjar and Mahfud in last place in the race to lead the world's third-largest democracy, just lagging another candidate Anies Baswedan, but well behind clear frontrunner Prabowo, whose running mate is President Jokowi's son.
On Tuesday, State Secretary Pratikno confirmed that Mahfud had made the request to him during a private meeting on Monday night.
Speaking after the second vice presidential debate in early January, Mahfud, the running mate of presidential candidate Ganjar Pranowo, said he would resign from the cabinet.
He then repeated the statement on the campaign trail.
“I have been planning to resign for a long time, since before the first presidential debate,” he said last week.
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