Manchester United will be without captain Wayne Rooney and midfielder Michael Carrick for the Europa League clash with Saint-Etienne on Thursday, while Phil Jones remains sidelined.
The trio missed training on Wednesday and Mourinho confirmed at his pre-match news conference that they would not be involved in the first leg of United's last-32 tie against their Ligue 1 opponents.
Defender Jones has not featured since limping out of the 0-0 Premier League draw with Hull City earlier this month, when he sustained a bruised foot.
Rooney and Carrick will sit out as a precaution, with an FA Cup fifth-round trip to Blackburn Rovers and the EFL Cup final against Southampton concluding United's February schedule either side of the return leg in France.
"Wayne and Michael, I don't want to say injuries because I don't think we are speaking about injuries," Mourinho said.
"We are speaking about little problems and protection for these problems, so they are out."
To offset Jones' ongoing absence, Mourinho revealed Marcos Rojo would be fit to play, having missed out on the 2-0 weekend win over Watford, but the Argentina defender will not start.
"My team is playing well and I'm going to stick with [Antonio] Valencia, [Eric] Bailly, [Chris] Smalling and [Daley] Blind," he said, confirming his starting back four.
Mourinho conceded United's ambitions amount to more than participating in Europe's second-tier competition but pointed towards the valuable experiences that could be in store for his squad during the latter stages.
"The Europa League is not a competition we want to play in but we show it respect," he said.
"We cannot choose competitions so we play competitions to win. And I think it's also a good way to give the team, as a team, experience.
"I think European experience is always a plus."