Tusk said the risk of a break-up was real and that there was a need to handle the negotiations over Britain with care.
"After my talks today with President Iohannis, Prime Minister Cameron and President Hollande and before meeting Prime Minister Tsipras, Prime minister Sobotka and Chancellor Merkel tomorrow, I have only one political reflection. This is a critical moment," Tusk told reporters after a meeting with Romania's President Klaus Iohannis.
"It is high time we started listening to each other's arguments more than our own. The risk of a break-up is real because this process is indeed very fragile and must be handled with care. What is broken cannot be mended."
Tusk said that Britain's membership in the EU was at stake.
"At stake is also the future of our European Union, where we will all have to decide together and where we cannot and will not compromise on European values."