The woman became unwell just after 7pm on Saturday and was taken to Queen Alexandra Hospital where she later died.
The man was found collapsed around half an hour later, also dying at Queen Alexandra Hospital later that evening.
The annual two-day festival, which was celebrating its fifth year, is held in King George V Playing Fields in Cosham, Hampshire.
Acts including Dizzee Rascal, Craig David, Sean Paul and British actor Idris Elba were due to headline over the weekend.
Organisers said they were cancelling events as a “safety precaution”.
In a statement on Facebook they said: “The safety of our amazing customers has always been paramount to us and so to keep everyone safe and in respect to those who have passed, we have taken the decision not to open today.
“As you can imagine, this decision was not taken lightly and was taken with the support of the local statutory authorities who we continue to work with.
“Enquiries are being made into the circumstances of what has happened, but we must reiterate our advice to all our customers to responsibly dispose of any substances.”
Police officers and dogs are now at the site investigating the circumstances of each death, which are being treated as separate incidents. Neither is being treated as suspicious.
At around 9pm on Saturday Mutiny Festival shared a post on their Twitter page entitled “Harm prevention alert” which said: “Festival family – we are aware of a dangerous high strength or bad batch substance on site.
“We strongly urge you to not take any substances whatsoever and to report any symptoms of illness / discomfort immediately to medical, welfare, security or the safeguarding team.
“Please stay alert and look out for each other.”
In response to the post, Hampshire Police told Sky News: “We are aware of the alert issued by the festival and are looking into its content.”
The festival organisers had also said earlier that they were “devastated to hear of the tragic loss of life from its festival family”.
The message shared on Facebook said the organisers would work with authorities. It urged participants to “drop your loved ones a call or message to let them know you are ok”.
Hampshire Police have asked anyone with information to call them on 101.