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: