Dene Magna School in Mitcheldean, Gloucestershire, has about 750 pupils on its roll.
Headteacher Stephen Brady said: "It's just got worse and worse - we had to send 26 pupils home today, sometimes common sense has to rule."
A private cleaning firm will begin a deep clean on Friday to sterilise the school ahead of it reopening.
The school normally has an attendance of 97%, with fewer than 20 students off in a day, but on Thursday this had fallen to 80%.
"We've had a steady increase in the number of students and staff coming down with this. I think we've been hit with what is a perfect storm of bugs," Mr Brady said.
"Some of the students have experienced nausea and sweating, others with vomiting and diarrhoea."
He also said a supply teacher had come in for one day but was forced to go home, after falling ill within a matter of hours.
It is expected that the pupils will recover from the bug within 72 hours.
"My only message is with the students don't let them go out and about at the weekend," added Mr Brady.
"If you can keep them in so they don't spread this amongst their friends.
"A good wash would go down very well so they can be back on Monday, nice and healthy."

Anthony Storrie died on 30 June 2013 at the Royal Alexandra Hospital in Paisley after taking "N-bombs".
The 26-year-old had been arrested the night before for an alleged police assault while under the influence of the drug, which is now illegal.
A fatal accident inquiry heard he had suffered damage to his liver while "crashing about" in his flat.
Sheriff Principal Duncan Murray ruled there was no evidence Storrie, of Paisley, had been assaulted by police officers or his friends.
He said: "The N-bomb caused Mr Storrie to be in the agitated state.
"The effects of the N-bomb then prevented him from being able to give any explanation of the injury which he had sustained.
"Nonetheless, Mr Storrie's death would in all probability not have occurred had he not taken N-bomb.
"Mr Storrie's death is a stark reminder of the risks posed by drug-taking.
"It is clear from the evidence presented to this inquiry that N-bomb is a potent compound producing significant hallucinogenic effects.
"It is also apparent from the evidence given by experienced consultants in emergency medicine of the significant risks posed to those taking cocktails of drugs in uncertain dosages and of uncertain chemical composition or purity."
Drugs expert Dr Richard Stevenson had told the inquiry that the effects of the drug would have made it impossible for Storrie to properly describe his injuries.
He said Storrie was in a state of "excited delirium" when he was admitted to hospital and was suffering from a range of physical phenomena which contributed to his death.
The inquiry heard the cause of death was recorded as "blunt force trauma" stemming from a cut to the liver which was caused by an abdominal haemorrhage.
The trauma and injuries including broken ribs were caused by a blow "the equivalent to being kicked by a horse or driving at speed in a car without a seatbelt, crashing and hitting the steering wheel".
Dr Stevenson, an A&E doctor at Glasgow's Royal Infirmary, said Storrie's symptoms meant he was "about to die" when he was taken to hospital for treatment.
He said that by taking the hallucinogenic drug, which is similar to LSD, he had "life-threateningly low" blood pressure, a racing heart, and an increased body temperature.
A school has been forced to close until Monday after more than 145 pupils and staff came down with a sickness bug.
[NEXT_CONCEPT]
A man who died in police custody would still be alive if he hadn't taken a so-called legal high, a sheriff has ruled.