Brentford make two changes to the side that drew 0-0 with Leeds last Sunday.
Yoane Wissa replaces Mads Roerslev up top while Aaron Hickey comes in for Kristoffer Ajer in defence.
Brentford XI: Raya, Hickey, Pinnock, Mee, Henry, Norgaard, Jensen, Dasilva, Mbeumo, Toney, Wissa.
Southampton make four changes to the side that lost in the EFL Cup semi-finals to Newcastle on Tuesday.
Romain Perraud, Samuel Edozie, Mohamed Elyounoussi and Romeo Lavia come into the starting XI.
Lyanco, Kyle Walker-Peters, Carlos Alcaraz and Adam Armstrong all drop to the bench.