Police were called to Chapel Street in Prahran at around 1.30am following reports a man had been stabbed during an altercation.
The victim, aged in his 20s, was taken to hospital, however he died shortly after.
It is understood the altercation began outside of Love Machine nightclub.
A crime scene has been established and Chapel Street is closed between High Street and Greville Street
No arrests have been made and an investigation is now under way.
Anyone with information is urged to contact police or Crime Stoppers on 1800 333 000.
