South African Airways (SAA) said it was cancelling 200-odd flights on Friday and Saturday following a strike call by unions over the cash-strapped national carrier's retrenchment plan.
The state-owned airline on Monday announced a restructuring process that could affect 944 employees and "lead to job losses".
"South African Airways has asked passengers who had been booked to travel on all its domestic, regional and international flights on Friday and Saturday not to turn up at airports," the carrier said in a statement late Thursday.
SAA spokesman Tlali Tlali told AFP about 200 flights would be cancelled over two days.
The airline, which employs more than 5,000 workers, is one of the biggest in Africa, with a fleet of more than 50 aircraft providing dozens of domestic, regional and European flights each day.
But the company is deep in debt, despite several government bailouts, and has not recorded a profit since 2011.
More than 3,000 workers, including cabin crew, check-in, ticket sales, technical and ground staff, are expected to take part in the open-ended strike from Friday, the unions said.
The unions are pressing for a three-year guarantee of job security and an eight percent across-the-board wage hike.
Pilots - who are not taking part in the strike - have accepted a 5.9-percent increase, they said.
The unions said "inflated contracts" outsourcing work were "crippling SAA's finances (and) literally bleeding SAA dry every day."
Finance Minister Tito Mboweni announced in February that the government would reimburse the company's 9.2-billion-rand ($620-million) debt over the next three years.
South Africa is struggling to get its state-owned companies back on track after nine years of corruption and mismanagement under former president Jacob Zuma.