Paolo Sousa and Leonardo Jardim are the early frontrunners to replace Mark Hughes after Saints parted company with the Welsh manager.
Hughes’ last match in charge was Saturday’s 2-2 draw with Manchester United as Saints failed to hold on for the win after taking an early 2-0 lead at St Mary’s.
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Southampton have announced that assistant first-team manager Mark Bowen and assistant first-team coach Eddie Niedzwiecki have also followed Hughes in leaving the club.
“We would like to express our thanks to Mark and his staff for all of their efforts during their time at St Mary’s,” read an official statement. “The search for a new manager to take the club forward is already under way.”
Former Queens Park Rangers and Leicester City boss Sousa was spotted at Saints’ match against Fulham last month – leading to speculation that he was being lined up as a potential replacement.
Jardim has a better recent record, having led Monaco to the Ligue 1 title two years ago before getting the sack after a poor start to the current campaign.
Saints have confirmed that first-team assistant coach Kelvin Davis will take charge for Wednesday’s Premier League game against Tottenham Hotspur at Wembley.