The Portuguese defender required stitches in the injury picked up in the defeat by Manchester City at the weekend.
"Jose is not fit for tomorrow. He still has the cut above his knee with the stitches," Koeman told a news conference.
"We are hopeful that he can play this Saturday, but tomorrow is too early."
Koeman's side have lost their last two league games but he thinks Wednesday's clash with Liverpool is the ideal opportunity to get back to winning ways.
"It's very important because Southampton only have two opportunities to win a title, the FA Cup and the League Cup, so it's important because we want to reach the semi-finals and secondly, after the two defeats the best way to get back full of confidence is winning," he said.
"It's a great game to play tomorrow, it's sold-out, Liverpool are doing well under a new manager.
"Every game against a big club is a nice challenge."
Koeman has a lot of respect for Liverpool's new manager Juergen Klopp, but said time will tell how the German is regarded amongst Liverpool fans.
"Admiration is not a good word, I think respect is the best word for him," the Dutchman said. "He had a great time in Dortmund, is an experienced coach and he has taken the challenge of Liverpool, a big challenge.
"Only the future will tell if he is the right person, but it looks positive at the moment but football can change," he added.
Liverpool have won six of their last seven matches in all competitions.
(Reporting by Martyn Herman, editing by Ed Osmond)
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