The 28-year-old Spanish international had surgery last month and Mourinho told the club website on Friday that he would not be fit until "late May."
The final Premier League games are scheduled for May 21, with the Europa League final, should United reach it, being played in Stockholm three days later.
Mourinho also said central defenders Phil Jones and Chris Smalling, who were injured on international duty with England last month, will not return to the squad until mid-May.
The pairing of Eric Bailly and Marcos Rojo have been at the heart of the defence in the absence of the English duo and the Portuguese boss is concerned with their accumulation of fatigue before United host league leaders Chelsea on Sunday.
"There is nothing I can do (about the current defensive situation)," said Mourinho. "They (Bailly and Rojo) have to go until the limits.
"If we arrived in a situation in the Premier League... where mathematically the top four is not possible, then it's an easy decision... rest them and go with them in the Europa League - if we are still in the competition."
Read the full article on eurosport.co.uk: Mata set to miss rest of season after groin surgery