De Gea fumbled a tame Cristiano Ronaldo strike into the net late in the first half of the enthralling 3-3 World Cup draw between the teams on Friday.
That goal completed Ronaldo's brace and the Portugal star sealed a hat-trick with a stunning 88th-minute free-kick to earn his side a draw in the Group B clash.
Mourinho – who was helped to a second-place finish in the Premier League by De Gea's heroics at Manchester United – said the 27-year-old would be well aware of his error.
"De Gea is my boy," he told RT .
"It hurts me to say it but he knows it was a bad mistake. It's a mistake he doesn't make with us at Manchester United because he was named player of the season for fantastic performances.
"But that happens to the best."
Despite leading thanks to a Diego Costa double and Nacho Fernandez's fine strike, Spain were forced to settle for a draw after Ronaldo's late heroics.