Claude Puel has indicated he is set to ring the changes again for Monday's trip to face Everton.
Saints travel to Goodison Park for their first match of 2017, as they look to recover from back-to-back home defeats, against Tottenham and West Brom.
The clash with Everton will be the team's third game in just six days, and Puel says the rigours of that schedule mean changes will need to be made again.
"It's not the same for the opponents," he said. "For example, West Bromwich had five days between their two games, and for us it's just three days. Then we play another game against Everton just two days afterwards.
"We are the only team playing three games in six days. I think it's not normal, but it's important to keep the good attitude and now to correct this for the next game.
"I think other players, fresh players can work for the game against Everton, and together we've got to correct this and give a good reaction."
Puel will definitely have to replace Virgil van Dijk in his line-up at Everton, after he received a one-game ban in his sending off during the closing stages of the 2-1 defeat to West Brom.
"Virgil is very important for us, of course," he said. "It's a bad scenario. It's the same scenario as the last game, against Tottenham, with the red card for Nathan Redmond, and now it's Virgil, but it's important in this difficult period to keep our calm and the good concentration.
"It's very important for the next game and the other games. It's important to keep a clear idea and a good spirit and to give a good reaction."