Number of reasons..
1) Father being ill - been mentioned already but his dad has had brain surgery and this has then been followed by a pnuemonia setback. for any person who is close to their parents this is a devastating blow.. but for a guy like Jose, his career is non existent without his father's influence.
2) Hasn't won the champions league in 7 years and not likely to for some time..
For a guy who has had the ambition of being the best manager of all time, it must be a huge blow to not have made the three cup mark yet and a greater blow still to see someone like Carlo get to the three cup mark first.
3) Deification of Pep - Mourinho always had something against Barca, but Pep has become the human symbol for all his hatred for Barca and then some. It must irk him hugely to know that Pep is combining both winning/beautiful football, is adored by the media, is possibly tactically ahead of him as a coach and could win more CL's than him. Until he is vanquished.. no way can Jose be happy.
4) Marital frustrations/location issue.. we know he has had affairs in the past. Being away from the missus and cooped up in a hotel, his family all the way in London. I am doing the same thing, am in London with family back in Birmingham and it does eat away at you.. you don't feel settled. He needs to get his wife to come to Manchester.
5) Hasn't had full control of a team since Inter - this is a big one, arguably the biggest one that has wore him down. He's gone from total control at Porto, strong control at Chelsea (although this wasn't quite complete control - he must have thought it was an anomaly), total control at Inter.. to barely any control at Madrid (you can't ever get total control at a club like that) and then to another lack of full control situation at Chelsea (where incidentally, I don't think he actually wanted to be there.. it was the United job he really wanted). It must irk him that being such a proven manager when he is given full control, that at this stage of his career he still has to fight to be given full control.
6) The Rooney situation/squad situation - No doubt that he is fully aware of this situation but he must be annoyed that he is having to be political and play a game. Contrary to beliefs, whilst Jose is a master at playing mind games and getting what he wants eventually.. in reality, he is a simple guy and very meritocratic. He just wants to be able to pick what he considers the best XI for United. If he feels his hands are tied in any way, which they are currently.. he will feel aggrieved.
7) Not knowing if he still has it - this must also be playing on his mind. In his heart of hearts, he probably believes in point 5, that he hasn't been given a proper chance for a long while to build his own team with his type of characters/players. That said there must be that element of fear that maybe the problem is him and not the situations he finds himself in. He can't afford to think like that, because then he basically isn't the special one anymore.