The commemorative fixture will take place at St Mary’s on Saturday, March 28, with promotion winner Barnard set to return to St Mary's as a player.
The now-retired striker made 73 appearances for Saints between 2010 and 2014, scoring 24 times and helping the club return to the Championship.
Valencia played 339 games for the Red Devils. He is a former Europa League and two-time Premier League winner and played 99 times for Ecuador.
José Fonte, Victor Wanyama and Rickie Lambert are among the other players already confirmed for the clash at St Mary's.
Saints Legends will host a Manchester United Legends team in March. (Image: Southampton FC)
Man United’s team includes former Premier League winners Dimitar Berbatov, Louis Saha and West Brom, with world-renowned football icon Bryan Robson as boss.
In addition, Andrew Surman and Jos Hooiveld have also been confirmed for Saints, with Ronny Johnsen and Danny Simpson set to feature for United.
The fixture is part of the club’s celebrations marking 50 years since Saints lifted the FA Cup for the first and only time against Man United in 1976.
Supporters attending will hear from members of Saints’ 1976 FA Cup-winning team, who will share memories from the famous Wembley triumph.
Tickets are priced at £20 for adults and £10 for children, with seats available in the Itchen and Northam stands. Away supporters will be in the Kingsland.