The Italian will leave as manager after Sunday's season finale against Manchester United.
De Zerbi said: "We have agreed to end my time at Brighton so that the club and I can continue to work in the way that suits each of us best, following our own ideas and visions, as well as our work and human values.
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"Leaving now provides me with time to take a break before deciding on my future plans.
"I am very sad to be leaving Brighton, but I am very proud of what my players and staff have achieved with the support of everyone at the club and our amazing fans in the past two historical seasons."