The hosts have gone with the same team that ran out 2-0 winners against Crystal Palace on Monday.
Meanwhile, Reading manager Brian McDermott has made one change to the side that beat Brighton in midweek.
Tomasz Cywka is out of the starting lineup, while Jay Tabb comes into the midfield for the visitors.
The Saints go into the match above second-placed Reading at the top of the table by virtue of goal difference.
Southampton: Davis; Butterfield, Fonte, Hooiveld, Fox; Chaplow, Hammond, Cork, Llalana; Sharp, Lambert
Subs: Richardson, Harding, Do Prado, Martin, De Ridder
Reading: Federici; Cummings, Pearce, Gorkss, Harte; McAnuff, Kebe, Mullins, Tabb; Roberts, Hunt
Subs: McCarthy, Gunnarsson, Le Fondre, Church, Afobe