Several roads including North Street and Pavilion Gardens have been cordoned off by police and forensic officers have been combing the scene.
Sussex Police said a local man in his 20s was discovered at around 2.30am in East Street, close to the junction with North Street, with serious injuries.
He was taken to Royal Sussex County Hospital in Brighton for emergency treatment for chest injuries, where he remains in a critical condition.
The incident is being investigated as a suspected stabbing, and police are appealing for witnesses.
Read here for pictures of the scene: Brighton’s North Street and Pavilion Gardens closed by police after incident
Detective Chief Inspector Andy Wolstenholme, from the Surrey and Sussex Major Crime Team, said: “We are treating this as an isolated incident and there is nothing at this stage to suggest there is a threat to the wider community.
“There will be an increased police presence in the area this morning, and our enquiries are ongoing to establish the full circumstances and trace those responsible.
“A section of North Street will be closed for some time to enable us to carry out further examinations, and I’d like to thank the public for their patience and understanding at this time.
“We’re urging anyone with any information – specifically if you saw or heard anything in the vicinity of Royal Pavilion Gardens in the early hours of this morning – to come forward."
Anyone with any information is urged to report it online or call 101, quoting Operation Martello.
You can also contact the independent charity Crimestoppers anonymously on 0800 555 111 or report it online.