The midfielder has withdrawn from Serbia's squad with an unspecified injury.
He will now miss his nation's upcoming Nations League fixtures against Montenegro and Romania.
Matic's injury also means the chances of him facing his and Mourinho's former side at Stamford Bridge on October 20 are now in the balance.
The 30-year-old has appeared eight times for the Red Devils so far this season and played the full ninety minutes of Saturday's stunning comeback from two down to defeat Newcastle.
Now he could be forced to sit out the bumper showdown with the Blues after arriving back at United's Carrington HQ for treatment.
The ace, who spent a total of five years at Chelsea during two separate spells, initially reported for duty with Serbia before returning to his club.
Matic won two Premier League titles and the EFL Cup while at Stamford Bridge before reuniting with Mourinho at United in July 2017.
More to follow…
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