Greater Manchester Police said 19 people were confirmed dead and roughly 50 were injured by the explosion at Manchester Arena. Emergency vehicles were helping the injured and bomb disposal units were later seen outside the venue.
The blast is "being treated as a terrorist incident until police know otherwise," Manchester police said in a tweet.
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The venue, Manchester Arena, tweeted that the incident occurred "outside the venue in a public space."
There was mass panic after the explosion at the end of the concert, which was part of Grande's The Dangerous Woman Tour. The singer was not injured, according to a representative.
Britain's terrorist threat level has been set at "severe" in recent years indicating an attack is highly likely. Police said the explosion is being judged a terrorist attack unless new information proves otherwise.
Witnesses reported hearing two loud bangs coming from near the arena's bars at about 10:35 p.m. but there were few further details.
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"A huge bomb-like bang went off that hugely panicked everyone and we were all trying to flee the arena," concertgoer Majid Khan, 22, told Britain's Press Association. "It was one bang and essentially everyone from the other side of the arena where the bang was heard from suddenly came running towards us as they were trying to exit."
Added Oliver Jones, 17: "The bang echoed around the foyer of the arena and people started to run."
Video from inside the arena showed concertgoers screaming as they made their way out amid a sea of pink balloons.
Numerous police cars, ambulances and riot-equipped officers were seen rushing to the arena, which holds 20,000 people.
Grande's "Dangerous Woman" tour was at Chicago's United Center in March. The Manchester appearance was part of her continuing world tour that runs until September.
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Twitter users reported they thought it was a "gunshot" or "bomb," but some speculation is the panic may have been a speaker that blew up at the end of the show.
Managers for Grande, 23, said she is OK and unhurt by whatever it was that caused the crowd to panic.
Britain's National Rail Service said that Manchester Victoria Station right next to the arena has been evacuated and that trains are "unable to run."
Facebook activated its Safety Check. Chicago police said they are in touch with their federal partners and said, "At this time, there is no nexus or known threat to the Chicago area but as always, we encourage individuals to report any suspicious activity to 911. Our thoughts and prayers go out to all of those affected by this horrible tragedy."
The Associated Press contributed to this report.