Police were called to the Runcorn area at about 10:50 BST amid concerns for the teenager's welfare.
Evidence suggests she had taken the substance Vertex, Cheshire Police said.
Four people treated in Warrington yesterday were also thought to have taken the legal high - although one is no longer being linked to the substance.
The girl was later discharged from hospital after treatment.
Assistant Chief Constable Mark Roberts said: "We are extremely concerned that this substance would appear to have led to a number of people being hospitalised in a serious condition.
"I would strongly urge people not to take this substance, and for people to be aware of the dangers of taking any substance known as a legal high."
A 16-year-old girl has been taken to hospital after taking what police believe was a legal high in Cheshire.