A solitary Che Adams goal handed the hosts all three points at St Mary's, as the Saints capitalised on a defensive error in the first half.
However, Guardiola accepted that mistakes are simply part of the game, adding he was pleased with City's overall performance, which had everything but the elusive leveller.
"The mistake was a mistake but it's part of the game," he said in his post-match press conference.
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"We didn't lose because of this reason. It’s happened many times - these kind of situations.
"Look at the amount of chances we had. It's football. We tried to score goals.
"In general, mentally, the games we played have been more than good - but it's not enough to win.
"We cannot say we are a not a team who scores goals this season. We are leading in goals and we create a lot of chances.
"I am so proud. I like the way we played but it's not enough. It's not a complaint of the players. Far from it."
Watch Pep Guardiola's post-match press conference in the video above...