The pair were rushed to hospital in a critical condition after falling ill at Reminisce Festival in St Helens last night.
Officers say a number of other people have also been taken to hospital with suspected overdoses and are currently being treated by medical staff.
Cops believe the individuals have taken MDMA – or ecstasy – tablets but say enquiries are ongoing to confirm this.
The festival issued a warning on social media about a "bad" batch of blue diamond pills circulating the event on Saturday.
It said: "We love to see you having an awesome time at Reminisce, but be safe! There has been information about some 'bad' blue diamond pills.
"If you are concerned about you or a friend approach some help from stewards or present to one of the onsite medical centres."
Detective Inspector Paul Grounds said: "These are the early stages of our investigation but I want to reassure those affected that we are doing everything possible to identify exactly what substance or substances have resulted in these severe reactions, working alongside the health service.
"We initially believe that ecstasy tablets were taken by some of those in hospital but this is all subject to further enquiries.
"I would urge anyone else who has had an adverse reaction to any substance make themselves known to medical services as soon as possible.
"Likewise, if you are still in possession of any drugs from the event, please do not take them under any circumstances but let us know and we will recover them for further enquiries to be made.
"We are also working to identify who was responsible for supplying these tablets so please come forward with any information.
"You may be worried about being in trouble for taking illegal drugs, however our immediate priority is to ensure that nobody else is affected by these tablets.
"If you have family and friends who attended the festival, ensure they are safe and well and report any concerns to medical services immediately.
"We want to hear from people who know who supplied these drugs or from those who took the drugs and experienced an adverse reaction. You can come forward directly to police or anonymously to Crimestoppers on 0800 555 111."
Anyone with information can contact @MerPolCC, call 101 with reference 333 or @CrimestoppersUK on 0800 555 111.
Reminisce Festival is an annual event that started in 2014 and features some of the world's top dance and house DJs, who play everything from old skool classics to current hits.
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