A 33rd-minute strike from Sadio Mane was enough to secure all three points for Southampton, with the Senegal winger thumping home the rebound after Graziano Pelle's low drive had come off the post.
Southampton hammered Sunderland 8-0 in the Premier League last weekend and Hughes felt his side were wary of that result given the manner in which they performed in the first half at St Mary's.
He said: "From our point of view we're a little bit disappointed with the first half performance.
"We didn't really ask enough questions of Southampton and made it a little too easy for them and showed them a little too much respect, which is understandable to a certain extent given their exploits here last week.
"Second half I thought we were a lot better. We made a change very early on, got Mame Diouf on, and that gave us a threat in behind and that stretched the game and allowed us to get control again.
"I think second half we were the better side but we never really created the clear-cut chances needed to get back on level terms."
Consistency has been something of a problem for Stoke, whose only win on the road so far this season came at champions Manchester City back in August.
The two sides meet again in the League Cup on Wednesday and Hughes vowed to attack Ronald Koeman's side, who are now second in the Premier League.
He said: "Southampton are a good team. They're on a high at the moment, they're winning games and confidence helps in that regard, but I didn't think there was too much between both teams today.
"We're a team that's in mid-table and Southampton are in the top end but there wasn't a great deal of difference between the teams.
"We play them again on Wednesday and the apprehension that we possibly showed in that first half certainly won't be there, so we'll look to be really positive."