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Nani was named in the starting Xl against Columbus and was originally shown a yellow card for a challenge on Artur.
But it was controversially upgraded to a red card following a VAR review.
The decision provoked a furious reaction from the Orlando players and Nani couldn't hide his emotions, leaving the pitch in tears.
Columbus scored an equaliser moments later but Benji Michel grabbed a late winner to secure 10-man Orlando the points.
Nani, who spent seven years at Old Trafford, joined Orlando in 2019 and has become an integral player, scoring 19 goals in his first 55 appearances.
It's not the first time Nani has struggled to hold back the water works.
Five years ago, he recalled breaking down at United during a particularly difficult time.
He told The Players' Tribune: "There was one period when I wasn't playing well. The fans weren't happy with me. Sir Alex [Ferguson] wasn't happy either. I was so angry with myself.
"One day it actually got to the point that I broke down crying. I went to Pat [Evra], who was doing muscle recovery in the jacuzzi at the training ground, and I just began to pour out all my frustration.
"I was like, 'Pat, why isn't my hard work paying off? Pat, why are the referees always against me?' And then I began to psyche myself up. I was like, 'Pat, I'm gonna turn this around! I know how strong I am! I'll show them!'
"Pat just sat there and listened. Then he got up, hugged me and said, 'I know. I know. The fans will love you again. You'll soon be scoring goals again. You are one of the best players I have seen, Nani. I have no doubt about this. No doubt.'
"About a week later, I scored an amazing goal against Chelsea. Suddenly I was playing my best football. Everyone was happy. My confidence was back.
"Soon after that, Pat came over to me, looked me in the eyes and said, 'That's my boy!' It was such a great moment."
Nani also let the tears flow in 2013 when he was sent off in a Champions League defeat by Real Madrid at Old Trafford.
The 26-year-old was dismissed by Turkish referee Cuneyt Cakir half an hour before the end of the game, an incident that turned the tie the way of the Spanish team.
Nani was distraught in the United dressing room at full-time and later made an emotional phone call home to a long-term mentor in Portugal.
"Nani was inconsolable," a source said. "He was on the phone to Portugal sobbing, asking people if they thought he had done anything wrong."
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