Claude Puel has confirmed that Virgil van Dijk's ankle injury is a long-term problem and cast doubt on the likelihood of the defender playing again this season.
Van Dijk sustained ankle ligament damage during Southampton's 3-0 win over Leicester City in January and has not played competitively since then.
The Saints have struggled in the Dutchman's absence, losing five of their last seven games in all competitions, and with Chelsea rumoured to be interested in signing Van Dijk at the end of the season the 25-year-old may have played his last game for the club.
When asked whether Van Dijk might be in contention to return to the squad for Saturday's Premier League match against Bournemouth, Puel said: "It's not possible.
"It's a long injury and we will see if he comes back before the end of the season."
Puel will also have to do without Manolo Gabbiadini, who has yet to recover from a groin injury sustained during the 2-1 defeat at Tottenham last time out.
"I think that Gabbiadini cannot play this game," said Puel. "He is not available, but we will see for the next one."
Puel added that the international break had left him with work to do in assessing the fitness of his squad, saying: "Of course, for us, it's a little difficult because we have had 15 international players for this break.
"It's a good thing for them and the club, but difficult for the staff to work and prepare this game for Bournemouth."