The 18-year-old talent was injured in the 2-0 defeat to Real Madrid at the NRG Stadium in Texas.
A tackle from teammate Casemiro saw Brazil star Rodrygo land on him resulting in Mainoo being substituted.
Christian Eriksen replaced him in just the sixth minute of the friendly and he was then spotted on crutches.
And now Manchester United have announced the players is set to miss the start of the new season.
A statement read: "Manchester United can confirm that Kobbie Mainoo suffered an ankle injury during the match against Real Madrid on Tour 2023.
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"The midfielder is expected to be ruled out for the first part of the 2023/24 season.
"He has flown home from Tour to the UK where further assessment of his injury will take place before a medical decision on the next steps.
"Kobbie was handed his fourth start in pre-season against Real Madrid when Brazilian forward Rodrygo landed on his leg following a tackle from United midfielder Casemiro.
"The Academy graduate was forced to withdraw from the match."
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Mainoo posted on Instagram: "I'll be back stronger and in no time," he wrote. "Thanks for your messages of support."
New Red Devils captain Bruno Fernandes replied: "I'm waiting you on the pitch soon."
And Alejandro Garnacho added: "Soon back bro, you are the best."