The 24-year-old had been in a critical state after collapsing on the field 20 minutes into a reserve game against Genk on Monday.
He was given emergency treatment on the pitch before being rushed to hospital where he was placed in an induced coma in an effort to save his life.
Mertens began his career at the country’s most successful club, Anderlecht, before moving to Lokeren in January last year from Cercle Bruges.
He had been capped several times by Belgium at U21 level.
Lokeren said in a statement on their website: “Today something happened which no one could ever dare to predict. Much too soon, we are saying goodbye to Gregory Mertens.
“We are a football club. Everyone in and around the club lives and breathes football. But suddenly something happens which makes us realise football is just football. Today is such a time.”
This is the second tragedy suffered this year by a young Belgian footballer following the death of 20-year-old Junior Malanda of German Bundesliga side Wolfsburg who died in a car crash in January.