The £10m summer signing was unmarked six yards out in the centre of goal as he met a Ryan Bertrand cross six minutes from time with Saints trailing 1-0 at White Hart Lane.
Mane fluffed his effort and Saints were defeated by former manager Mauricio Pochettino and their run of six straight wins in all competitions came to an end.
Koeman, though, was in no mood to blame Mane.
"It's part of football," he said.
"Sometimes you score and sometimes not.
"He had two good chances in this game, in the first half a good one as well and the second half a good one.
"He was playing good, he was fast, he was doing his best and missing chances is part of football."
For the big stories and the banter follow us on Twitter: @tribalfootball