The charges stem from the discovery of a 19-year-old man with serious injuries on Langhorn Road on Sunday, July 24.
He was taken to the hospital with a puncture wound to the lower back and abdomen and later died.
Ken Mulangala, 20, of Southampton’s Warren Avenue, has been charged with murder.
Jordan Gregory Matthews, 20, of Bursledon’s Estridge Close, has been charged with murder.
Donovan Neil Thomas, 35, of London’s Norwood High Street, has been charged with murder.
Billy McIntyre, 23, of Southampton’s Millbrook Road East, has been charged with assisting an offender.
They have been remanded in custody and will appear in Southampton Magistrates’ Court tomorrow (July 29).