Villa took the lead twice through Gabriel Agbonlahor and Libor Kozak but Saints levelled matters through Jay Rodriguez then Dani Osvaldo.
But the hosts won it with a stunning strike from Fabian Delph ten minutes from time, consigning Saints to a first home defeat of the season.
And gaffer Pochettino was left scratching his head at full-time having seen the team concede three goals for the second time in the space of four days.
“Overall our possession was good and we managed many phases of the game tonight, but we also made some errors at the back and were not as solid as usual,” he said.
“We have been very solid so far this season, but that was not the case tonight.
“We were unlucky in the fact that they created four chances and scored three goals – we created 21 chances.
“We just lacked intensity at the back and we weren’t solid,” Pochettino continued. “We were heavily punished for that.
“It seemed like we had the game controlled, but when they scored that third goal from outside the penalty box it was all over from that point.
“I think overall we made a really great effort, but it just wasn’t our night.”
After three consecutive defeats, Saints will now look to bounce back against Manchester City when they come to St Mary’s this weekend.
“Of course we will try and stop this bad run of results,” insisted Pochettino.
“I think both results against Arsenal and Chelsea were undeserved, and again in this game we were unlucky and didn’t deserve defeat.
“We will try our best on Saturday to try and stop this bad run that we are on.”