It was to no avail and Aguero wrapped up victory with two more. 5-1, min. 90, Aguero.
With 48 minutes gone, and the score level at 1-1, De Bruyne played a give and go with Sterling on the left wing and cut inside.
Manchester City have written to the body in charge of professional referees to raise their concerns over a series of risky challenges suffered by their players, according to widespread reports on Saturday.
The Foxes did an excellent job of clogging up the middle of the field and forcing the hosts to resort to playing on the edges and playing in many crosses.
As some pointed out, City's bench did include academy graduates Brahim Diaz, who came on, and Tosin Adarabioyo, while the 21-year-old Oleksandr Zinchenko was also named, showing that Guardiola's bench did have a youthful feel to it.
De Bruyne picked out Raheem Sterling at the back post to put the home side ahead in the third minute, with Sterling converting from nearly an identical position to where he had missed against Burnley last weekend.
Aguero got his second goal in just five minutes in the 53rd minute.
On one hand, the winger could well be motivated to show what the Premier League leaders have missed out on and his presence would add quality to the Foxes ranks.
The Belgian provided a hat-trick of assists for City and De Bruyne is now the best creator in Europe. Schmeichel attempted to pass a ball to his defense, but Aguero intercepted the weak offering.
The Manchester City legend wasn't done at three.
The Foxes went into the half-time break level at the Etihad, but were blown away by a four-goal blitz from Sergio Aguero in the second half, with Puel admitting it had been a hard evening for his side.