Mwepu played in all six of Brighton's opening Premier League games this season but fell ill while on international duty with Zambia during the recent international break and has not played since.
He joined Brighton from Red Bull Salzburg last summer and made 18 appearances in the Premier League, scoring two goals and providing four assists.
Mwepu's condition has been described as heriditary and his risk of developing a cardiac arrest is high if he continues playing.
Mwepu made 23 appearances for the Zambia national team and scored six goals.
In an emotional statement on Twitter, Mwepu wrote: "A boy from a small Zambian township called Chambishi has some news to share.
"He stood strong to follow his dream of playing football at the highest level, and by the grace of God he lived his dream by reaching 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. This is however not the end of my involvement with football, I plan to stay involved in some capacity.
"I would like to take this opportunity to thank everyone that supported me in my football journey, including my wife and family, my agent 12MAN, the Zambian FA, all my previous clubs, teammates and coaches, and specially everyone at Brighton and Hove Albion."
Seagulls chairman Tony Bloom has told the club’s official website: “We are all absolutely devastated for Enock. He and his family have had a traumatic few weeks and while we are just thankful he has come through that period, he has seen such a promising career cut short at such a young age. 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.”
Brighton boss Roberto De Zerbi added: “I am so sorry for Enock. Before I arrived I looked at all the squad, and he was a player I was so excited and looking forward to working with. We will do everything we can to help him.”
