The Whites return to top flight action against the Saints this weekend following the October international break.
Ralph Hasenhüttl's men are expected to play two up front, which usually sees Bielsa opt for three at the back in a formation switch.
Last season's top goalscorer Patrick Bamford has been ruled out already while key midfielder Kalvin Phillips is racing to be fit.
“Bamford won’t play and Kalvin has chances of being able to do so," Bielsa told his pre-match press conference.
'[Bamford] has a problem in his ankle and his recovery is subject to the evolution of the injury. The evolution we have is day to day.
"[On Phillips] we will decide today, tomorrow and Saturday."
Luke Ayling remains sidelined as does long-term absentee Robin Koch but Adam Forshaw is once again fit and available for selection.
Whites winger Raphinha faces a race against time to be included at St Mary's with Brazil in action in the early hours of Friday morning.
Given what we know about Southampton's tactics and the latest team news - we expect Bielsa to move to a more fluid 3-3-1-3 with two changes likely on the south coast.
Here's our predicted Leeds United line-up against the Saints:
7. Phillips - CDM
Bielsa said he had a "chance" to play after a calf strain ended his England involvement. Sounded positive - he's a key cog in the machine.
8. Klich - CM
A wonderful assist for Poland on Tuesday. Finding some form and feels like the best option in the 3-3-1-3 here.
9. Harrison - LW
It just feels like too much of a tight turnaround for Raphinha after his Brazil exploits. Expect Harrison to start in the second change, with James on the other flank.
10. James - RW
His best performance since his move to Elland Road last time out. Looked like he was all over the place, causing huge problems. Photo: Getty
11. Rodrigo - ST
Bamford is out again so Rodrigo will get the nod. Could do with a goal for his confidence. Photo: Getty