Brazilian midfielder Guly do Prado, who scored 23 goals in 118 Saints appearances in a four-season spell, will leave the club, along with Jonathan Forte and Lee Barnard.
Cody Cropper, Lloyd Isgrove, Sam McQueen, Omar Rowe and Jake Sinclair have been offered new contracts having been involved with the first team this season.
A number of players from Southampton's Development Squad and Academy have also been informed that they will not be offered new contracts at the end of their current deals.
From the Development Squad, Matt Young, Joe Curtis and Andy Robinson will depart the Club as their professional contracts will not be renewed, while Jamal Branker and Fraser Colmer have also been informed they will be released at the end of their three-year scholarships as they will not be offered professional terms.
Under-18s Charlie Higgins and James White have reached the end of their two-year scholarships and have not been given pro deals.
Corby Moore has joined newly-founded North American Soccer League side Indy Eleven after being informed his professional contract would not be extended. Tom Leggett and Isaac Nehemie have joined Aston Villa on professional terms.