Fulford School in York, which has around 1,300 pupils, will remain closed to everyone except children of key workers and children who are classed as vulnerable until the end of term.
In a letter to parents, headteacher Steve Lewis said 28 people have tested positive for Covid-19 since Friday and “this has resulted in over 500 children needing to self-isolate”.
He also revealed that 35 members of staff are self isolating.
“I regret that we have had to close the school to pupils for the remainder of the school year,” he said.
“It is always a difficult decision to close a school, especially following the 18 months of disruption our pupils and parents have experienced.
“However, the safety and well-being of all within our school community is our highest priority and the decision to close was made on these grounds.
“All lessons are now being delivered via MSTeams. The school day will follow a similar pattern to that of our previous lockdown.”
Covid-related pupil absence in schools in England has hit a new record high since all students returned to class in March, Government figures show.
Around 11.2 per cent of state school pupils did not attend class for Covid-19 related reasons on July 8. That is up from 8.5 per cent on July 1.
There were 747,000 children self-isolating due to a possible contact with a Covid-19 case, 35,000 pupils with a suspected case of coronavirus and 39,000 with a confirmed case of Covid-19.
Under the current rules, if a pupil in a bubble tests positive for Covid then the whole group must self-isolate at home, but that rule will be dropped on July 19.
Speaking earlier this week, Prime Minister Boris Johnson said that July 19 is the right time to ease coronavirus restrictions because of the “natural firebreak” of the school holidays.
He said: “We also know if we were to now delay this fourth step, for instance to September, or later, then we would be reopening as the weather gets colder and as the virus acquires a greater natural advantage and when schools are back.
“We think now is the right moment to proceed when we have the natural firebreak of the school holidays in the next few days.”