A section of Guildford Road, between Liverpool Road and Manchester Road in Fratton has been blocked off.
Police were called by paramedics at about 2.20am today.
The ambulance service had been sent to Sackville Street in Southsea to the seriously injured man, who was taken to Queen Alexandra Hospital but later died.
However, a focus of this morning’s investigation is in Fratton, where police believe the man may have been assaulted earlier in the night. Police are also looking at nearby Sandringham Road.
They have appealed for information and have asked anyone who knows anything to call 101 and mention Operation Lighter.