Pupils and teachers at a Mpumalanga high school left the premier in shock when some ran amok as if possessed and others collapsed during his visit there.
Some of the children injured themselves running blindly into the school fence.
Premier Thabang Makwetla was visiting the Lusushwana High School in Bettysgood near Ermelo when the incident happened. He was accompanied by education MEC Mmathulare Coleman
The school management could not explain the actions of the children and teachers, saying that it was as if "they were possessed".
Makwetla said he was "shocked".
"We will send psychologists and spiritual counsellors to the school to deal with the situation," he said.
Government officials, including VIP protectors, were forced to assist when about 50 pupils started screaming, collapsing and running around as if they were being chased. The same happened to four teachers.
Ambulances and health workers were called to assist.
Makwetla was addressing the pupils and teachers when the incident happened.
Makwetla has visited six other schools in the Gert Sibande, eNkangala and Ehlanzeni regions as part of a drive to support schools.
Nomvula Kininda, a Grade 10 pupil who was affected, said: "A similar incident took place at the school in October last year, affecting more than half of the pupils."
Authorities said they held prayers and the situation normalised.