The Belgian has struggled with injuries of late but when fit, he is one of the best there is as proved against Crystal Palace over the weekend.
Elsewhere, Leicester City officially secured their Premier League status with a 3-0 win at home to Watford.
United are four points further back in fifth ahead of their trip to sixth-placed Arsenal on Sunday, with Mourinho set to ring the changes as the match falls in the middle of his team's Europa League semi-final with Celta Vigo.
Sergio Aguero has 31 goals this season and Guardiola believes City's campaign would have been different if young Brazilian Gabriel Jesus, who has scored 4 goals in four league starts, hadn't missed over two months with a broken toe.
"It's normal, someone that's been successful that many times, you have one season where it's not going your way and people want to focus on it - that's what creates news and creates entertainment".
"I did not expect to see what we saw in the second half, which was very disappointing because we'd fought back into the game and were keeping Manchester City at bay".
"Even the next champions, Chelsea, we create more chances here (at the Etihad Stadium) and even at Stamford Bridge, but in the boxes we are not good".
Crystal Palace boss Sam Allardyce: "Defensively we made too many mistakes and they punished us heavily".
Guardiola's stats are correct - Spurs had 13 shots to City's 12 when they lost at White Hart Lane in October. If you do things right you can get opportunities to score, as long as you frustrate them.
"Vincent helps us with his presence to be better in our box, but in the box of the opponent we are not good".
Discussing the difference in City's performance in the first and second half, Kevin De Bruyne - another of City's goalscorers, along with David Silva, Raheem Sterling and Nicolas Otamendi - commented: "We scored our chances in the second half". When it comes to scoring goals, Manchester City manager Pep Guardiola says you have to pay to play. There are four unbelievable teams fighting for the final two places. It makes a difference to have the next two games here.
Speaking after the game, Kompany welcomed the uplifting effect the big win would have on the team's morale.
'It's a possibility that we've been warning them about, ' said Allardyce.
"Manchester City, normally when they beat you here, produce outstanding skills but we gifted them easy chances to score and they thrashed us".
"Hopefully United can focus on the Europa League and forget a little bit about the Premier League and then next season we can have five English teams in the Champions League, which would be incredible". That is the biggest disappointment.