Long is set to miss out once again with a broken metatarsal picked up at Middlesbrough, while Jeremy Pied may be in contention for a start as Soares is struggling to shake off the effects of the injury he suffered in the goalless draw against Manchester United on Wednesday.
Bertrand, who missed the game against United, may also miss out, meaning Matt Targett could keep his place, while Charlie Austin is pushing for his first start since December.
The St Mary’s crowd will be hoping for a better spectacle than the goalless reverse fixture this season, which saw Marko Arnautovic sent off.
It could be manager Claude Puel's final game in charge amid reports Southampton are considering replacing him.
Although Southampton reached the final of the EFL Cup, they failed to progress to the knockout stages of the Europa League and will finish the Premier League season with their lowest points tally in four years.
Frenchman Puel signed a three-year deal last summer but it has been reported that Southampton's match against Stoke will be his last in charge.
His season-long performance will be reviewed by executive director Les Reed next week.
"I am under contract and I am comfortable with Southampton," Puel said. "My work and my wish, is just to stay concentrated about this last game and finish well.
"We have an opportunity to finish up in the table and it's a good thing after this long and difficult season. We are lucky about this and that is the most important thing."