Jerome (ankle) and Vignal (hip) missed the 0-0 home draw with Stoke on Saturday and are injury doubts ahead of the trip to Southampton.
If they are unfit Stuart Parnaby and Kevin Phillips could retain their places after starting Saturday's game.
However, McLeish could also hand a starting role to record signing Christian Benitez who has been restricted to three appearances as substitute since moving to St Andrew's earlier in the summer.
Lee Bowyer returned to the starting line-up against Stoke after completing a three-game suspension for his sending off against Preston.
Blues (from): Hart, Carr, Queudrue, R Johnson, Vignal, Larsson, Ferguson, Fahey, McFadden, Jerome, O'Connor, Maik Taylor, Phillips, Benitez, McSheffrey, Parnaby, O'Shea, Carsley, Bowyer, D Johnson.