It was a nightmare return to Amex Stadium for Graham Potter as he watched his old club suffer a heavy defeat.
Leandro Trossard's calm finish put the home side in front after Thiago Silva surrendered possession cheaply in his own half.
The first of the two own goals came from a Solly March corner and the second came from a Pervis Estupinan cross.
Two minutes after the interval, Kai Havertz nodded in a cross from Conor Gallagher to give the visitors hope, but they couldn't find a way to get back in the game.
Potter and his players were left ruing the fact that Mendy parried Enciso's shot into the German's path after he had replaced Arrizabalaga.
The victory lifts De Zerbi's side up to seventh.
All eyes were on Potter as he took charge of his first game in over a month. His mood will not have been helped by his team's defensive horror show on the south coast as he was booed by large sections of the home fans.
Silva almost gifted the home side an opener when his attempted cross-field pass was cut out by Moises Caicedo, but the veteran centre-backtoned for his mistake with a superb goal-line clearance after Trossard had tried to chip Blues goalkeeper Arrizabalaga.
The Brazilian prevented Estupinan's strike from crossing the line, but it was his poor pass that allowed Kaoru to set up Trossard for the game's opening goal.
From the visitors' perspective, the second and third goals were self-destructive. After Estupinan's delivery was guided past his own keeper by the somewhat unfortunate Chalobah, Loftus-Cheek inadvertently steered Gallagher's flick-on into the net.
In the first half, they had opportunities of their own, with Christian Pulisic firing wide from a promising position and Robert Sanchez tipping Gallagher's loopinghead past the post, but Havertz's headed goal early in the second half didn't spark a revival.
Havertz should have been able to cut the deficit further, but he missed the target. The counter- attack by Gross rubbed salt into the wounds of the other team.
The damage was done before the half-time break and Potter will take some solace from that.
There's more to come.
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