The youngest victim among the at least 21 people who died at a drinking place at the weekend was 13, police minister Bheki Cele has said.
The cause of the deaths was not immediately clear and the authorities are investigating.
The victims were found strewn across floors and tables at the Enyobeni Tavern in the town of East London.
The bodies were taken to mortuaries, where post-mortem examinations will be carried out.
Mr Cele, who had visited the scene and was briefed by the local police, said those who had died were between the ages of 13 and 17 - but a detailed list of the victims has not yet been produced. The legal minimum drinking age in South Africa is 18.
There are reports that people who had gone to the tavern were celebrating the end of school exams.
South African President Cyril Ramaphosa expressed his "deepest condolences" to families of the victims.
"This tragedy is made even more grave by its occurrence during Youth Month - a time during which we... advocate and advance opportunities for improved socio-economic conditions for the youth of our nation," he said in a tweet.
Oscar Mabuyane, premier of East Cape Province where the tragedy happened, did not give possible reasons for the deaths, but condemned the "unlimited consumption of liquor".
Speaking at the scene, he said: "You can't just trade in the middle of society like this and think that young people are not going to experiment."
The incident occurred in the early hours of Sunday.
A provincial safety official told AFP news agency that a stampede had been ruled out as the cause of death as there were "no visible wounds".
"Forensic [investigators] will take samples and test to see if there was any poisoning of any sort," Unathi Binqose said.
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