It is understood the investigation is related to an envelope with white powder received by Lagan College.
The school, on the outskirts of south Belfast, said the PSNI are investigating “an issue”.
The school contacted parents via text message to tell them that the investigation is taking place at “the front of the school site”.
It said that students and staff are safe but that “no member of the public can access the site at present to go out or come in”.
Amanda McNamee, the school’s principal, said the school day is continuing as normal while the police probe continues.
Fire crews with ‘bio suits’ are currently examining the envelope.