Claude Puel says Cedric Soares and Jose Fonte won’t face Espanyol but Nathan Redmond and Pierre-Emile Hojbjerg are tipped to play.
Saints are preparing for their first game at St Mary’s since the end of last season on Wednesday night with Puel keen to get his summer signings involved to familiarise themselves with their new surrounds.
Fans will get the chance to see winger Redmond and midfielder Hojbjerg ahead of the opening game of the Premier League season against Watford next week.
And Puel will take to the home dug out for the first time since he replaced Ronald Koeman to coach Saints against the visiting La Liga outfit.
But Soares and Fonte, who were given extra time off to recharge their batteries following Portugal’s victorious Euro 2016 campaign, will watch on from the stands.
Puel said: “For Espanyol it’s not possible as they’e just come back to the training sessions.
“It is important we don’t exhaust these players.
“Perhaps you will see them for the friendly game against Bilbao (on Sunday August 7), we will see their level on the pitch to see if it’s a possibility or not.”