Rooney did not play in either the opening draw in Russia or Monday night's fiery defeat to Chelsea amid reports that he had come off worse in an accidental training ground collision with Phil Jones. Fellow forward Martial, meanwhile, was introduced as a second-half substitute against Rostov but was then ruled out of the FA Cup quarter-final loss at Stamford Bridge due to injury.
Such a double blow contributed to a full-blown striker crisis that left most believing that Marouane Fellaini would be deployed as a lone frontman against Chelsea, although Marcus Rashford eventually ruled himself fit despite a bout of illness.
Zlatan Ibrahimovic is currently serving a three-match domestic suspension after he accepted an FA charge of violent conduct relating to his elbow on Bournemouth defender Tyrone Mings, but remains eligible for continental duty.
Likewise Ander Herrera, who was controversially dismissed at Chelsea for two fouls on Eden Hazard and will now miss two Premier League outings following his second red card of the season. Eric Bailly is back in contention after completing a one-match European ban.
"Rooney is injured," Mourinho said of his skipper during a pre-Rostov press conference held on Wednesday. "He had some kick in his knee area, so he can't even come out to the pitch. He stays inside the medical department."
On Martial, he added: "Martial was injured for the Chelsea match. He couldn't be selected for the Chelsea match and, if you are injured for the Monday night game, it's because you're injured for the Tuesday morning training session.
"And if you are injured for the Tuesday morning training session, it's not because of today that you can be able to play on Thursday. So he's out of my mind. I don't think about him, we have the same players we had in the last match plus Ibrahimovic returning to the Europa League."
Rostov, level in the tie after an excellent second-half goal from Aleksandr Bukharov cancelled out Henrikh Mkhitaryan's close-range effort on a dismal pitch at the Olimp-2 Stadium that has ironically now been deemed unfit for purpose by the Russian Premier League's Natural and Artificial Turf Pitches Commission, are likely to be without Vladimir Granat for the trip to Old Trafford after he exited the first leg with a shoulder injury.
Captain Alexandru Gatcan and veteran midfielder Timofei Kalachev will also miss the game through suspension, with Mourinho particularly pleased by the latter's absence following an influential performance in Rostov-on-Don.
"I think it's good for us that he doesn't play. I think they have solutions and they tried that solution in the last match against Terek Grozny. They played the other boy, I think Igor Kireyev, in Kalachev's position and he did well. But Kalachev is experienced, hard, big mentality, so I think he's a player that they miss."
Addressing reports that United made the delayed five-hour trip back from London by coach on Monday night and did not return to Manchester until 04.00 GMT after their plane failed to arrive at Heathrow Airport on time, Mourinho, already exasperated by a hectic fixture pile-up, said: "At 12:00 they were here to train again, as the great professionals they are, with the great commitment they have and the fantastic group of boys that I work with.
"We had two gifts. We thought one gift was enough. The first gift was to play Monday night, the second to play with 10 men and the third was to have a promenade on the M6. But we are professionals so the next morning we were here to train and today the same."