A Welsh Ambulance Service spokesperson said it was called to the scene shortly after 01:30 BST.
The air ambulance also attended.
Police said the families of the two males who died are being supported by specially trained officers.
Newport councillor Alex Pimm said details of the incident remained under investigation.
“Rumours are circulating on social media about what has happened and I urge people to refrain from speculation, to allow the authorities to carry out a full and thorough investigation.
“Two young lads have lost their lives, and my condolences are with their family and friends at this extremely sad and difficult time,” he said.
Alice Walters, 35, said her friend lives on the road where the incident took place.
“She saw the police tape when she woke up and it made her feel ill,” she said.
