Manager Chris Wilder said his Sheffield United squad needs "a bit of a shake-up" after their slim survival hopes were dealt another blow by Southampton.
The 2-0 defeat at Bramall Lane left the bottom-of-the-table Blades 12 points from safety with 10 games of the season left.
"There's so many things we need to address," Wilder told Sky Sports.
"We need to keep our best players. There's a couple who need to go. They have to go at the end of the season."
He added: "I'd like to shake it up quicker. We looked like we'd run our race."
United were without eight players through injury or suspension, including defenders Phil Jagielka, John Egan, Chris Basham, Jack Robinson and Jack O'Connell.
"The hand I'm getting given at the moment is a tough one, with some of the players we have to go with," said Wilder, whose future at the club remains unresolved.
"I haven't really got an answer for anybody. We have to regroup and go again. It's a tough gig."
United rarely troubled Southampton goalkeeper Fraser Forster, and Saints would have won by a more handsome margin had Takumi Minamino, Nathan Redmond or Che Adams - who scored a spectacular goal early in the second half to add to James Ward-Prowse's first-half penalty - converted several good opportunities late on.
"We didn't deserve anything from the game," said Wilder. "They could have had three or four.
"We have to be at our best. The best players have to be playing to the best of their ability to be able to make it a tight affair or get a result.
"We looked off it and tired in the second half."
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