The former PSG centre-back has missed a handful of games recently with a muscle issue, with the game against Newcastle on Monday deemed to soon for a comeback.
However, in the two fixtures thereafter, the Blues take on Atletico Madrid in the Champions League before facing Man Utd at Stamford Bridge the weekend after, so Silva might just be kept fresh for those games as three in just over a week is a lot to ask for a 36-year-old
Should Silva be left out or on the bench, a back three of Cesar Azpilicueta, Andreas Christensen, and Antonio Rudiger should continue.
Since being appointed as Chelsea boss, Tuchel has given most players a chance to impress but now is the time for him to start deciding on a favoured starting XI.
That will likely lead to a midfield pair of Jorginho and Mateo Kovacic again, with Marcos Alonso and Callum Hudson-Odoi on the flanks, though Reece James is pushing for a start on the right ahead of his compatriot.
Tammy Abraham suffered a nasty-looking ankle injury against Newcastle on Monday, and although the issue is not as bad as once feared, with no ligament damage, he will likely not be able to shake off the problem before the Southampton game.
Werner broke his drought with a close-range finish versus the Magpies, so will be eager to kickstart a goalscoring run.
Kai Havertz could be available again, but continues to be a minor doubt with a muscle injury.
As for in goal, Kepa kept a clean sheet against Newcastle and didn't really put a foot wrong, so it would be a surprise if Tuchel opted to bring Edouard Mendy back in.