The 30-year-old contracted the virus while away on international duty with Morocco and returned a positive test before returning to the club late last week.
His absence was not the only coronavirus issue to hit Wolves in their build-up to the visit of the Saints.
Skipper Conor Coady also missed out on the game having spent close to a fortnight in self-isolation after coming into contact with someone carrying the virus.
It ended a run of 121 consecutive league appearances for Coady, who was just six games short of Phil Parkes’ all-time club record.
"It's a big blow. Unfortunately Coady and Saiss are not with us," said Nuno Espirito Santo.
"Coady has played since the Championship, a lot of games, and unfortunately this is how it goes with the current situation.
"Since coming back from the England squad he has been self-isolating. He has tested negative and already had the virus so maybe he's already immune. But he cannot be with us.
"Many things don't make sense and we have to keep on going. it's not a good moment for anybody.
"Saiss is in self-isolation since returning from the national team. He tested positive and is comfortable with the situation.
"He is at home by himself with the family in another room and he has to protect himself because we want him to return safe and healthy."