Mwepu became ill last month on a flight to join the Zambia national team squad in Mali and was treated in a hospital there. He had further medical tests in England.
“The condition, which can worsen over time, would put Enock at an extremely high risk of suffering a potentially fatal cardiac event, if he were to continue playing competitive football,” Brighton said in a statement.
The Premier League club said the health problem was not seen on previous cardiac screening tests, which top-level soccer players routinely undergo each season.
“We are all absolutely devastated for Enock,” Brighton chairman Tony Bloom said. “As a club we will give him all the love, help and support we possibly can to make a full recovery, and then as he decides on the next steps in his life.”
Mwepu said he had “lived his dream” by playing in the Premier League.
“Some dreams, however, come to an end, so it is with sadness that I announce the need to hang up my boots because of the medical advice I have received,” Mwepu said in a statement.
Mwepu made his debut for Zambia as a teenager while he was playing for Salzburg. He won four Austrian league titles with Salzburg and played in the Champions League on a team with Erling Haaland. He joined Brighton last year.
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