The New South Wales Premier has vowed to do everything she can to shut down Defqon.1, after two people died in suspected overdoses at the popular Sydney music festival on Saturday night.

Key points: A 23-year-old man and a 21-year-old woman died in hospital after collapsing at Defqon.1 on Saturday night

A 23-year-old man and a 21-year-old woman died in hospital after collapsing at Defqon.1 on Saturday night Three others are in a critical condition and 13 more attended hospital to be treated for drug-related issues

Three others are in a critical condition and 13 more attended hospital to be treated for drug-related issues The NSW Premier says the event is unsafe and should be shut down

Police said a 23-year-old man from western Sydney and a 21-year-old woman from Victoria died in Nepean Hospital after collapsing at music festival in Penrith about 9:00pm.

Three more festival goers remain in a critical condition in hospital.

Ms Berejiklian described the deaths as "absolutely tragic" and vowed to ban the event.

"I never want to see this event held in Sydney or New South Wales ever again — we will do everything we can to shut this down," she said.

"I don't want to see this ever happen again — young lives lost for no reason.

"I understand there were some deaths in the past, but to have at least two on one night when every assurance was given to those attending that it was a safe event — clearly it wasn't when so many people have succumbed."

Ms Berejuklian denied cancelling the event would force it and others to go underground, and said pill-testing at music events was "not a solution".

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"Anyone who advocates pill-testing is giving the green light to drugs. There is no such thing as a safe drug and unfortunately when young people think there is, it has tragic consequences," she said.

"I'm absolutely aghast at what's occurred [and] I don't want any family to have to go through the tragedy that some families are waking up to this morning — it's just horrible to think about."

Defqon.1 is an annual music festival playing mostly hardcore techno, house and trance music. It is has taken place since 2009 at the Sydney International Regatta Centre.

About 30,000 revellers attended this year's event.

In 2015 Nigel Pauljevic, 26, was found unconscious in a tent at the festival and later died.

Hundreds sought medical attention

Police said emergency services at the event responded to multiple reports of suspected drug overdoses.

A 26-year-old is in Nepean Hospital in a critical condition while a 19-year-old man was airlifted in a critical condition to Sydney's Westmead Hospital where he remains in intensive care.

A third person is also in hospital in a critical condition.

Police said 13 attended Nepean Hospital for treatment for drug-related issues, while up to 700 people sought help from medical staff at the music festival.

Police formed Strike Force Highworth to investigate the deaths and police are appealing for anyone with information to come forward.

'Police can only do so much'

NSW Police Acting Assistant Commissioner, Allan Sicard, said police had done everything they could to ensure the event was safe, with 180 uniformed and undercover police attending and 20 detectives on standby.

"What we can't do is be in people's heads, be in people's decision-making processes when they decide to take illicit drugs," he said.

"Police can only do so much."

He said it was too early to determine whether the same drug was responsible for the deaths and hospitalisations.

However he said toxicology tests were being fast-tracked and should be finalised within the week.

Ten people were charged with drug supply offences at the festival, including a 22-year-old man from Bankstown who was charged with supplying a prohibited drug, greater than a commercial quantity, after he was allegedly found with 20 packets of GHB.

The annual Defqon.1 festival is held at the Sydney International Regatta Centre at Penrith. (Facebook: Defqon.1)

A 33-year-old man from Mt Pritchard was also charged with supplying a commercial quantity of a prohibited drug after he was allegedly found with MDMA, while a 27-year-old man from Sydney was charged with supplying a commercial quantity of a prohibited drug.

Two teenage girls, both aged 17, were also charged with supplying a prohibited drug after they were allegedly caught carrying 120 capsules internally into the music festival.

A total of 355 drug searches were conducted with 69 people found to be in possession of drugs, including the 10 charged with supply offences.

Event organisers 'working with authorities'

In a statement, a spokesperson for the organisers of Defqon.1 said they were "deeply saddened by the tragic passing" of the pair and sent condolences to their families.

"We are disappointed at the number of reported drug-related incidents, we have a zero-tolerance policy in relation to drug use at the festival," the spokesperson said.

"Festival organisers are working closely and cooperating with the authorities regarding the fatalities and the number of medical presentations made during the evening, a full investigation is currently underway.

"As this is a matter with the NSW Police and the coroner and out of respect for the families and friends, we are not going to speculate on the cause of death."