Downend School in South Gloucestershire has closed to most pupils after 31 cases of coronavirus were identified among staff and students.
Year 7, 8, 9 and 12 have returned to remote learning for the rest of the week following advice from local health authorities.
A spokesperson for the school said: "Over the last few days, we have experienced a number of cases of COVID-19 within the Downend School community.
"This has meant that we have advised some students in Years 8, 9, 10 and 12 to self-isolate.
"We also have a number of staff who are confirmed cases and other staff self-isolating as contacts.
"We are working closely with the South Gloucestershire and South West Public Health teams, and are taking a number of temporary measures to contain transmission and prevent further spread of the virus.
"Due to the number of staff having to isolate, we have taken the difficult decision to move some year groups to remote learning for the remainder of the week.
"The safety of our students, staff and community is of paramount importance, and we will continue to monitor the situation carefully alongside our colleagues from Public Health."
As well as the partial closure, the school will be reintroducing face coverings in classrooms, corridors and communal areas for all staff and pupils as a precaution.