United's record signing suffered an ankle injury during Monday's training session at Nike's plush HQ in Portland and was unable to join his team-mates as they went through their paces at CenturyLink field ahead of the friendly with the Seattle Sounders.
Although Berbatov's injury is described as 'a knock', at such an early stage of pre-season, manager Sir Alex Ferguson will not want to take any risks.
It is a blow for the Bulgarian though given how eager he is to impress after failing to even make the bench for last season's Champions League final.
Ferguson has already pledged not to involve any of this week's arrivals for the encounter against the MLS' best supported team, which is expected to attract in excess of 60,000.
That includes new keeper David de Gea, who looked impressive in training but may need to bulk up to cope with the rigours of Premier League combat, plus Phil Jones, already identified as a potential partner for Chris Smalling in the future, which Rio Ferdinand feels is a bit unfair to Jonny Evans
"You can't discount Jonny," said Ferdinand in a webchat with www.manutd.com.
"It's a bit out of order that people have been saying it's definitely going to be Chris and Phil.
"Jonny's also one of the most talented central defenders in Great Britain.
"I'm sure all three of them will be battling it out in the future to play in the centre of defence."
Ferdinand revealed that he has been approached about the potential for taking up a film role, although the 32-year-old is not interested in such a venture until his playing days are over.
The England international is very media savvy and he would have seen the scope for a picture when he joined respective skippers Nemanja Vidic and Kasey Keller for the pre-match coin toss at the top of Seattle's famous Space Needle.
More importantly, the match practice will take United's fitness forward another notch, although having pushed themselves through so many double training sessions, tiredness may be an issue against the Sounders.
The overall goals are much more protracted though, with Ferdinand feeling confident about United's chances of retaining their Premier League title.
"Definitely," he said. "We have got an experienced nucleus who have been here for four or five years and have won things consistently.
"That breeds confidence, which is invaluable.
"We have also added three hungry players who want to win trophies."