English publication 'The Daily Mail' reports that the England boss will ring the changes following his side's disappointing performance last time out against Slovenia.
Said source claims that Liecester City defender Harry Maguire and Spurs midfielder Harry Winks are both set to make their England bows, whilst West Ham's Aaron Cresswell will make his full England debut.
Jack Butland will be handed the gloves in place of Joe Hart, thought talismanic striker Harry Kane has told the boss that he has no interest in being rested for the game.
With Southgate expected to go with a system involving wing-backs, the former Middlesbrough boss must decide whether to give a full debut to Kieran Trippier down the right or whether to persist with Alex Oxlade-Chamberlain, with Kyle Walker expected to be rested.
Southgate made it abundantly clear after Thursday's game that England's performance had not been good enough and he is keen to use the game in Vilnius as an opportunity to experiment ahead of a tough run of World Cup warm-up games that will see England take on two of the pre-tournament favourites in Brazil and Germany.