Fire crews have been called to the scene as pictures on social media show huge flames and plumes of smoke.
Saint John Mayor Don Darling said on Twitter: "This is obviously a live event. when we know more, you'll know more".
New Brunswick city resident Bob McVicar wrote on Facebook that it felt like a "bed-shaking explosion".
The refinery was operating under a shutdown, meaning there were more employees than usual working at the time of the accident.
Irving Oil has confirmed that they are responding to a "major incident" at the Saint John, New Brunswick facility.
Saint John resident Doug Bruce said he was about five or six kilometres away from the refinery at the time of the explosion. "Praying for the safety of all involved".
Irving says on Twitter that the company is "actively assessing the situation" and will share more information when it becomes available.
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Residents across the city reported feeling the effects of the explosion.
Irving Oil exports more than half of that to the United States, and the refinery is a critical source of fuel for the Northeast energy market, CNBC reported.
A massive oil refinery blast shook this historic port city Monday, sending flames and black smoke high into the sky but causing only four minor injuries - and leaving officials relieved it wasn't far worse. "I heard a rumbling, roaring sound".
An explosion at a refinery in Canada's east coast has left residents shaken and concerned.
The explosion at around 10 a.m. touched off a fire and sent thick, black smoke pouring into the air.
He chose to drive by the refinery and said he was nearby when he felt the vibrations of what he assumes must have been a second explosion.