Officers say the 18-year-old suffered an adverse reaction and later died, after taking MDMA at The Warehouse in Byker, early on Sunday.
A 19-year-old man was arrested shortly afterwards and another two men aged 19 and 21 were arrested on Monday.
Both 19-year-olds have been released on bail, while the 21-year-old remains in custody.
All three were arrested on suspicion of supplying a controlled drug.
Police have urged anyone who was at the venue on Saturday night and took drugs to see a doctor.
MDMA forms the active ingredient in ecstasy pills.
Police have made further arrests over the death of a woman who took drugs at a Newcastle nightclub.