The 16-point gap between themselves and Barcelona is insurmountable, and in their current form they will struggle to eliminate the seven-point deficit with neighbors Atletico.
But Mourinho is a specialist in Europe. Real are 4/1 second favorites to win the Champions League with many bookmakers and if you like to bet on sports, they are surely worth a punt.
Mourinho has shown signs that he is feeling the pressure and his decision to drop club symbol Iker Casillas for defeat 3-2 defeat in Malaga was a clear illustration of this. It was the first time Casillas had been dropped for an important game in 10 years.
The Portuguese tactician was brought in to end Barcelona's domestic and European dominance. He achieved the first of his two objectives last season as Real ended Barca's run of three consecutive Liga titles, but the Champions League still remains.
Real have landed Manchester United in the last 16 in what is undoubtedly the most appealing tie on paper. Who can forget the last time these two powerhouses met when Ronaldo's Old Trafford hat-trick helped the Merengues to a 6-5 aggregate victory, despite a 4-3 defeat on the night? With the way both sides are defending this season, a similarly dramatic tie is by no means out of the question.
Mourinho got the better of Sir Alex Ferguson in 2004 when a late Costinha goal prompted jubilant scenes which included 'Mou' haring down the touchline to embrace his players as Porto knocked the Red Devils out at Old Trafford.
Madrid enter this tie as favorites and, of course, they will be able to unleash an ultra-motivated Cristiano Ronaldo who will be keen to show his old club just what they are missing. United have looked susceptible at the center of defense this season, and in Ronaldo, Mesut Ozil and Karim Benzema, Madrid have the players to punish them more severely than United's Premier League counterparts have at times this season.
Barcelona will be lying in wait, possibly as early as the quarter-finals. Mourinho's less talented Inter Milan side knocked out Barcelona over two legs in 2009 and there is no doubt he has the players at his disposal to do it again, should they meet in the latter stages. The gap in quality has closed when the two Spanish giants come head-to-head as we saw last season when Real won at the Nou Camp to all but seal the title.
Real have reasons to fear German sides Bayern Munich and Borussia Dortmund in the latter stages. Bayern have a fine record against the Spaniards and knocked them out at the semi-final stage last season, while Dortmund beat them in the group stages of this season's tournament.
But if Mourinho can iron out some of the issues he has in his squad - he recently claimed he has 'three rotten eggs' - straighten out his defense and foster the siege mentality that has served him so well over the years, the Portuguese could yet have the last laugh at Wembley come May 25.