Unbeaten leaders Barca went on to hammer second-placed Atletico Madrid 4-1 with a double from Lionel Messi at the Nou Camp in the late game and moved 13 points clear of third-placed Real after 16 games.
"It is practically impossible," Mourinho told a news conference about their title hopes.
"That's too much [of a gap] at this stage. Last year we had a 10-point advantage in February or March and we were able to maintain it.
"But if we can improve in the league it will serve to help us in the King's Cup and the Champions League."
Real have struggled to replicate their record-breaking performances from last year and have already dropped 15 points with three draws and three defeats, one more than in the whole of last season.
Barca have won every league game except for the 2-2 draw at home to Real back in October.
Real's surprise 2-1 defeat at Celta Vigo in a King's Cup last 16 first leg in midweek has led to renewed speculation that Mourinho will not see out his contract at the Bernabeu which runs until 2016.
"I have never seen a situation like this before, losing so many points, and having a team so far from its objectives," Mourinho added.
"It's new for me, but I am not about to give up. I am not going to make a drama of it. We will seek to finish the season in the best way possible.
"We have titles within our reach and we have to fight for them, but the league is almost impossible now."
After having seen off their closest rivals Atletico, Barca were keen to play down their points advantage over the Madrid clubs.
"Atletico and Real will continue to be there," Barca and Spain midfielder Sergio Busquets told Spanish television.
"It is a good advantage but there is more than half a league still to play. No one could have imagined it, but we must carry on doing what we are doing."
Busquets sentiments were not shared by beaten Atletico coach Diego Simeone.
"Barca play in a different league to the rest of us," the former Argentina international told a news conference after his side slipped nine points adrift in second place.
"We tried to be competitive, played to our strengths, and we did well for a large part of the game, but this is a boring league. With their firepower it is impossible.
"Messi is the best in the world. I am just pleased he is Argentine."
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