Mancini branded the fixture demands caused by the international fixtures "ridiculous" but did not hold his defenders - including midfielder Javi Garcia in a makeshift centre-back role - responsible for the Southampton defeat.
He said: "The fixtures are ridiculous sometimes, as we played on Saturday and then had six players who came back on Friday, and five who came back Thursday night.
"Sometimes it is impossible.
"Nastasic came back Friday and Kolo came back three or four days ago - plus the last time Javi Garcia played there, he played really, really well.
"On Saturday we played well in defence, but the problem was that we didn't give the defenders any help. They were left to play alone, and we conceded two goals the like of which I have never seen in my life."