The Spaniard suffered a dead leg in the Capital One Cup win over Liverpool at Anfield and sat out last weekend's 1-1 draw with Chelsea at the Liberty Stadium. And the 25-year-old looks set to miss the trip to St Mary's as he struggles to get over the knock.
Club captain Garry Monk has filled in during Flores' absence, impressing with his handling of Fernando Torres against the Blues. Laudrup admits he has no concerns if Monk remains at the heart of his defence alongside Ashley Williams. "Chico is very doubtful, he is still in lot of pain," said the Dane.
"I knew when it happened against Liverpool it was very serious. Normally when you have a dead leg you get up and play on but then it is sore for three or four days. So when Chico had to come off I knew he was hurt, he wants to play every minute of every game. It was looking like eight or 10 days out so he is very doubtful for this weekend.
"There is no point risking him for one game if he is not right because we have lots of games coming up over the next few months. Garry came on and did very well. He did well against Liverpool and he did well against Fernando Torres together with Ashley."
Swansea make the journey to the south coast in buoyant mood after beating Liverpool and securing a point against Chelsea, in stark contrast to the Saints.
Nigel Adkins' side are bottom of the table with just one win to their name, and the former Scunthorpe boss has admitted he is probably the favourite to be the first top-flight boss to lose his job this season. Laudrup knows Swansea cannot afford to be complacent with their hosts fighting for their lives.
"My players always have their feet on the ground but when you play the big clubs it is easier to perform," said Laudrup. "It's my job to get the players to maintain the focus. This is so important for Southampton because of where they are. They are one of the three new teams in the Premier League and it's a different level from the Championship.
"They score goals but they also concede a lot of goals and if you are letting in two goals in every game then you have to score lots just to get a point. I've seen them in a few games this season like Manchester United at home, and Fulham at home, where they deserved a lot more.
"We really want to win this game, Southampton really need to win it. When you need something you give your all, and maybe something more that you did not know you have. We have to be clever and make sure we we maintain our focus. If we do that then we have the quality to get something from the game."