A 14-year-old girl is expected to appear in the George Magistrate's Court on Wednesday where she faces a charge of murder.
In a statement, police spokesperson Captain Dumile Gwavu said the teen allegedly stabbed a 15-year-old boy in Tabata Street, Zone 9, in Thembalethu on Sunday.
The boy was taken to the Kuyasa Clinic where he died.
The boy cannot be named until his next of kin have been informed.
"The reason for the stabbing is not known and they are not in a relationship as boyfriend and girlfriend. The knife was recovered at the scene," Gwavu said.