Video footage shared on social media showed men mimicking planes at St Mary's and the Saints confirmed authorities had taken the details of two individuals.
Sala's body was recovered from a plane wreckage in the English Channel this week after the Piper Malibu aircraft that was carrying him and pilot David Ibbotson disappeared on 21 January.
Southampton asserted its intention to ban anybody found to be involved in taunting the travelling Cardiff fans.
A statement from the club read: "Southampton Football Club can confirm that two fans were detained and had their details taken by police during our match against Cardiff City on Saturday [Sunday AEDT].
"The club will continue to work with Hampshire Police to identify any individuals deemed to have made indecent gestures towards Cardiff supporters.
"Such behaviour has no place in our game and will not be tolerated at St Mary's. The club will be taking an extremely firm stance against anyone involved and intends to ban those supporters identified."
Tributes to Sala were paid before the match, which Cardiff won 2-1, with both sets of players observing a moment's silence.