Arsenal have enjoyed a productive festive period so far, recording 2-1 victories at home to QPR on Boxing Day and at West Ham two days later.
Their New Year's Day clash at St Mary's Stadium represents their third fixture in quick succession, and Arsenal boss Wenger concedes it is a difficult task to maintain their winning momentum whilst giving players sufficient rest.
"We have Southampton which is another game that will demand a high intensity and commitment, so I will have to look at how we recovered because we gave a lot in the last two games in 48 hours," he said.
"It's down now to the quality of the recovery.
"Rotation is a sensitive subject because you can destabilise your team with too much rotation.
"So you have to find the right numbers for rotating the team. Overall, you want to keep the balance of your team and as well refresh sometimes in the positions where players are a bit tired."
Tomas Rosicky made his first Premier League start of the season against QPR before being rested for the trip to Upton Park, and Wenger confirmed that the Czech midfielder would return to the fray on Thursday.
Wenger has a fitness concern over Danny Welbeck, whom he felt would be "short" for the game after sustaining a thigh problem at West Ham.
Olivier Giroud is still suspended following his red card against QPR so Alexis Sanchez could be in line to fill the central striking role, while the likes of Aaron Ramsey (hamstring), Mesut Ozil (knee), Mikel Arteta (calf) and Jack Wilshere (ankle) remain out.
Having confounded many pre-season predictions, Southampton head into the clash fourth in the table - above Arsenal on goal difference.
Ronald Koeman led his side to a spirited 1-1 draw with league leaders Chelsea on Sunday, while the south-coast club frustrated Arsenal for much of the pair's meeting just four weeks ago at the Emirates Stadium, won late on by Alexis Sanchez.
Despite the grit in those performances to go with Southampton's abundance of creativity, Koeman remains cautious.
"Maybe we can come and surprise people," he said. "Arsenal are always one of the top clubs in the Premier League because they have very good players like Sanchez, who can win games.
"We don't have those sorts of players, we're more about teamwork.
"The top four is not an obsession because I don't like to watch every weekend the table because it means nothing [until the end]."
Influential midfielder Morgan Schneiderlin – a reported January target for Arsenal among others – misses out through suspension, while Nathaniel Clyne (ankle) is injured and Emmanuel Mayuka has departed for the Africa Cup of Nations.
