A fire at a traditional initiation school claimed the lives of the two teenagers this weekend in the Qumbu Village as police have begun investigations into the matter.
This follows the deaths of two other initiates in the province this year with much of the season still to come.
The Eastern Cape Health Department's Sizwe Kupelo says 25 people, including traditional nurses, were also taken to hospital for treatment.
“Some people were treated for smoke inhalation and others were treated for burn wounds”, said Kupelo.
The cause of the fire is not clear, but authorities have warned against initiation schools continuing their practice during the drought.