Three-foot Simon died in the cargo section of a Boeing 767 after flying out of Heathrow to a new celebrity owner in the US, The Sun reported.
Simon was expected to outgrow his father Darius, whose length of 4ft 4 inches made him the world's biggest bunny.
"He was as fit as a fiddle. I've sent rabbits around the world before and nothing like this happened," Simon's breeder Annette Edwards was quoted as saying.
"Something very strange has happened and I want to know what. I've sent rabbits all around the world and nothing like this has happened before," Edwards said.
"The client who bought Simon is very famous. He's upset," she said.
Simon, a continental giant rabbit, was 10-months-old. Continental giants cost 5,000 pounds a year to keep. Edwards' rabbits are hired out at 500 pounds a time.
United Airlines said, "We are reviewing this matter".
An airport source was quoted as saying that the news of Simon's demise sparked panic among United Airlines staff.
United recently made headlines and remains under scrutiny following its treatment to the Vietnamese-American passenger, David Dao, who was physically dragged off an "overbooked" flight when he refused to give up his seat for United crew members on a flight from Chicago to Louisville.
Just days after the incident, it emerged that a bride and groom headed for their wedding were booted from a United Airlines flight here after they relocated to empty seats three rows up without permission.
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