Emergency services have rushed to the scene in the Belgian city.
At least five people are wounded after the residential building collapsed in the Paardenmarkt area, largely populated by students.
Dramatic pictures show a gutted apartment block with dozens of ambulances lined up on the street.
The explosion rocked a pizza restaurant on the ground floor and flats above around 9.30pm local time (8.30pm).
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Several people are still thought to be trapped underneath as rescue workers sift through the wreckage.
A police spokesperson said: “The explosion on Paardenmarkt possibly involved three residences. There are multiple victims.
“Details about the number and the severity to follow.”
The blast was most likely a gas explosion, local media report.