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Atletico received a corner just minutes into the second half and Ronaldo decided to have a chat with his goalkeeper just before it was taken.
The 37-year-old can be seen making a number of gestures to de Gea and TV cameras picked up on the exchange.
De Gea's main weakness is duels in the box, specifically from corners, and it looked like Ronaldo had a few words of wisdom.
It's likely Ronaldo was discussing how United would be able to counter once they'd cleared the corner, gesturing for the defence to push up higher once de Gea kicks the ball.
Fans have reacted to the duo's chat and they think Ronaldo playing manager while on the pitch is hilarious.
One commented: "You see they are teaching him."
Another said: "I laughed. Does de Gea not feel ashamed?"
A third tweeted: "Ronaldo will be a great coach some day."
While someone simply put: "This is not the first time Ronaldo will tell him to come out and claim a cross."
De Gea is one of the world's best shotstoppers but he does lack when it comes to playing out from the back.
Paul Pogba was frustrated with de Gea's distribution in Sunday's 4-2 win over Leeds United, with the pair exchanging words at Elland Road.
The 31-year-old recently said he is able to play with the ball at his feet and explained the quality of attackers in the Premier League makes it challenging.
"What a goalkeeper has to do is to stop goals going in; that's the most important thing," he told UEFA's official website.
"And then, if you have the talent or the quality to be able to play with your feet and have good vision, that's phenomenal.
"I feel very comfortable playing with my feet, playing out from the back, following the lead of my team, but it depends on the coach and the style of play.
"[With Spain we] play with a very high defensive line. I've played this way since I was in the youth teams. [At United] we try to play with a high line, but some players are very fast and very talented, and if the pressing is not good enough, you can have problems at the back."
Joao Felix gave Atletico the lead inside seven minutes at the Wanda Metropolitano and Diego Simeone's side dominated throughout.
They hit the bar once in either half but Anthony Elanga scored off the bench, against the run of play, to make next month's return leg at Old Trafford an intriguing affair.
Featured Image Credit: BT Sport