The 24-year-old Brazilian picked up a groin problem while training in Denver and will fly back to Manchester to continue treatment.
A statement on the club's website read: "As he [Rafael] was unlikely to participate in the remaining tour games, returning to the Aon Training Complex affords the best overall option for his recovery in time to continue pre-season preparation when the team returns."
Louis van Gaal's reign as United manager began solidly in the Colorado capital as they followed up a 7-0 rout of LA Galaxy by recording a 3-2 victory over Serie A giants Roma on Saturday.
But the Dutchman already faces a selection dilemma with the news that Rafael will not feature in any of United's two remaining US tour games, leaving part-time right-backs Phil Jones and Chris Smalling in contention for the role.
Another option is to adopt a 3-5-2 formation, with the versatile Antonio Valencia operating at wing-back - a system Van Gaal used to good effect when guiding Holland to the semi-finals of World Cup 2014.
Does the writer of this article mean that the only other option is to play with the formation that United have already been playing with? This sounds like a disaster!- manfist