A whole school year group and 24 staff members are self-isolating after a number of positive coronavirus tests.
There were six cases among pupils at Ysgol Gyfun Gymraeg Plasmawr, Cardiff, and with five of these in year eight (ages 12 to 13), it was decided the whole year group should self-isolate.
Two teachers and a learning support assistant also tested positive.
Years seven and nine are attending on alternative days for two weeks because of reduced staffing.
In a letter to parents, headmaster John Hayes said 24 members of staff had been in close contact with those testing positive during “the infectious period”.
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“Naturally, having so many staff in self-isolation places a huge strain on our ability to safely manage the school,” he said.
“I have reluctantly come to the decision that pupils in years seven and nine will alternate their time in school during the next fortnight to reduce the pressure on being able to safely staff the school.”
He said the situation “evolved hour-by-hour” over the weekend and apologised for the late notification.
The self-isolation period ends on Friday, 16 October.
Meanwhile, Denbighshire Council said 22 year six pupils and two members of staff at Christ the Word Catholic School, Rhyl, must also self-isolate until 14 October after a case there.
Two members of staff and 14 pupils from nursery and reception classes at Ysgol Bryn Collen, Llangollen, must also self-isolate until 14 October after a positive case.
On Anglesey, the council confirmed a case at a fifth primary school, with a pupil of Ysgol Parc y Bont, Llanddaniel Fab, testing positive.