Frenchman Jeremy Pied has suffered a snapped cruciate ligament in his knee, meaning Cuco Martina's Everton move is now in doubt.
It was reported last week that former Saints boss Ronald Koeman was keen to bring the right back to Everton, as back-up to Seamus Coleman.
Pied is now likely to miss the rest of the season, as he requires surgery to fix the injury. He will be out for a minimum of six months, meaning by the time he is back to full fitness, there may not be enough time for him to win a place in the side. It is a huge blow for Southampton, who have not enjoyed the best of starts to the season.
The 27-year-old was only signed at the start of this month by Claude Puel, to offer cover for Southampton's first choice right back, Cedric Soares.
Martina deal now questioned
Until the injury occurred, it was heavily believed that Martina would be linking up with Koeman, the man who brought him to the Premier League. The Curacao international is not in Puel's plans for the coming season and was set to be shipped out, in order to free up space in the squad.
Martina was only signed 12 months ago by Koeman, for a small fee of £1m. Everton were set to bid around £2.5m for the 26-year-old, meaning Southampton had made a profit on the full back after only a handful of appearances in the last year.
Puel open to different options
Speaking after the injury, Puel admitted he was not sure what the club would do in terms of Martina. The Frenchman said Southampton would wait and see "the seriousness" of Pied's injury but admitted that it "was a problem."
Puel must now decide whether to keep hold of Martina or replace him with another signing in that full back position. The new manager could also promote another young talent through to the first team as cover.