"Voting in favour of this motion will be tantamount to throwing a nuclear bomb," said a statement issued by African National Congress chief whip Jackson Mthembu ahead of Tuesday's vote brought by opposition parties.
"The removal of the President will have disastrous consequences that can only have a negative impact on the people of South Africa," he said.
"It will result in the entire cabinet having to resign which will lead to a collapse in government... It will plunge our country into complete political instability."
South Africa's economy slumped into a recession in the first quarter of the year while unemployment nears 26 percent.
Popular support for the ANC, which was swept to power in the first non-racial elections in 1994, slipped to 55 percent in last year's local polls -- its worst-ever election result.
"We are not blind to the grievances raised by our people including our partners," said the statement, referring to vocal criticism from the ANC's coalition allies.
It acknowledged the impact of an unpopular cabinet reshuffle at the end of March that saw respected finance minister Pravin Gordhan ousted and replaced with a Zuma loyalist.
The statement also recognised the controversy raging around Zuma and his relationship with the Gupta business family, and a tranche of leaked emails that point to a corrupt relationship between the two sides.
It described allegations that state organs had been corrupted as "serious and legitimate concerns".
But the statement added: "We are raising these issues now to show the ANC has been responsive."
Gupta family member Atul recently told the BBC that the leaked emails had "no authenticity".
"There is a higher probability of the vote being passed under a secret ballot (but) ultimately we think most anti-Zuma MPs worry a secret ballot will not be secret because of the involvement of the security services and numbered ballot papers," he wrote.
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