Southern's ankle has swollen up badly following an injury he sustained after scoring the second goal in Saturday's 2-0 home win over Birmingham.
He is rated as doubtful to recover in time to face the big-spending Londoners and Claus Jorgensen will definitely miss out as he begins a three-match ban, having been sent off against Blues.
New loan signing Krisztian Nemeth will go straight into the squad, and caretaker bosses Tony
Parkes and Steve Thompson are also hoping to sign a midfielder on loan ahead of the game.
Strikers Ben Burgess and Steve McPhee remain sidelined with knee injuries.
Martin Rowlands and Patrick Agyemang have joined QPR's long-term injury victims.
Skipper Rowlands suffered a cruciate knee-ligament injury during the win at Derby last time out and has been ruled out for the rest of the season.
Hogan Ephraim replaced Rowlands at Pride Park and will hope to keep his place in midfield.
Striker Agyemang last week underwent surgery on a thigh injury he sustained in training and will not be back in action until mid-April.
Rangers have been without midfielder Akos Buzsaky for the majority of the season with a knee injury, while frontman Rowan Vine has been out since last April with a broken leg.
Centre-half Kaspars Gorkss returns to Bloomfield Road for the first time since he joined Rangers in the summer.