The midfield duo were forced off during Tuesday's UEFA Champions League win away to Bursaspor and are set to undergo scans to determine the severity of the injuries.
Nani was replaced during the first half due to a groin injury, while Fletcher hurt his ankle in the second period after earlier giving United the lead.
With Ryan Giggs working his way back to fitness, and Darron Gibson and Anderson having been laid low by a virus, United's midfield options are set to be depleted for the visit of Wolves.
"Unfortunately, Nani has a groin injury and is out for Saturday," said United boss Ferguson.
"I think Darren will be out as well, so that part has been disappointing.
"It is disappointing, but these things happen in football.
"We may have Darron Gibson back after a bout of flu, but Anderson has had a virus as well and I don't think he will be ready."
Man. Utd v Wolves.
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