Goalkeeper Marc-Andre ter Stegen was on the receiving end of ironic cheers from the fans in Washington DC after his blunder gave the United States a 2-0 advantage.
Further goals from Clint Dempsey and Jozy Altidore's opener laid bare some worrying defensive deficiencies which Low says are not preoccupying.
"We had made many changes and only had two training sessions before this game so mistakes happen," he said.
"Normally, we have (Mats) Hummels and (Jerome) Boateng. We made mistakes because we stood off our opponents too much.
"I'm not worried at all."
Not even the third international appearance of ter Stegen ruffled Low's feathers as he took the number of goals he has conceded in a Germany shirt to 10.
"He's usually a goalkeeper who is very good and secure at the back, and he's a good footballer too," said the Germany coach.
"He made a mistake, of course, and it was a shame for him, as it was for us.
"On the other hand, he made a few good saves. We had always planned on letting him play the full 90 minutes."
Away from the susceptible defence, which also conceded two against Ecuador last week, Low was particularly pleased with the first two caps of Freiburg forward Max Kruse.
Kruse showed no signs of nerves and scored a goal which made it 4-2 not long after taking to the field.
"He pleased me in both matches, absolutely," said Low.
"We were even more of a goalscoring threat with him in the team in both games.
"He moved well and got a goal too. He has definitely convinced me in these two games and training too."
Kruse, who moves from Europa League participants Freiburg to Borussia Monchengladbach this summer, can therefore expect to feature in Low's next squad selections for a friendly against Paraguay in August and the World Cup qualifiers against Austria and the Faroe Islands in September.