Manager Claude Puel told reporters on Monday that the Portuguese international defender would not be available for the match at St Mary's.
"Jose doesn't participate in this game," said the Frenchman. "We will see for the next game but, for the moment and with the situation of Jose, it's important to keep the stability in defence.
"We don't know the future for Jose. It's a difficult situation with the (transfer) window."
Puel said Southampton had given the 33-year-old "the possibility to study different opportunities," adding that while he respected the player's position the situation was proving a distraction.
News that makes sense
Your trusted source for staying up-to-date with the world around you. Get free daily news updates and analysis, straight to your inbox.
Fonte, who joined the south coast club from Crystal Palace in 2010, was not selected for last Saturday's FA Cup third round 2-2 draw against second-tier Norwich City at Carrow Road.
"It's difficult to play and have the good concentration with this situation," said the manager, who has appointed Virgil van Dijk as captain in Fonte's absence.
(Reporting by Alan Baldwin, editing by Neil Robinson)
