Daniel Jimeno Romero, 27, from Madrid, became the first person to be gored to death at the event in nearly 15 years when he was cornered by the bull.
And a 20-year-old man from London was one of six victims still being treated in hospital after he was gored in the left thigh by the animal, according to Spanish authorities.
A 61-year-old American who suffered serious injuries was also being treated in intensive care.
Mr Romero was gored in the neck after one of six bulls on the half-mile course separated from the pack, becoming frightened and aggressive.
Soon after the incident a man was pictured lying on a stretcher with his face and neck stained with blood and his eyes half-open.
Comedian Andy Smart, who was taking part in his 52nd run, witnessed the events.
He saw the brown bull, called Cappuccino and weighing 1,130lb, as it began to cause havoc.
He said: "This morning was quite hairy. The bulls were very fast.
"They are bred to be short and stocky and fast and they were flying.
"They must have been doing about 30kmh when they passed me.
"They go through the crowd like a knife through butter."
He said Cappuccino attacked two American men right in front of him about a third of the way along the course.
"It caught one of them and then stopped and went back to try and gore him.
"One of the men had blood on his head where he had banged it on the cobble stones. The other one was winded. I think he was trodden on by another runner."
Mr Smart, 50, from Portsmouth, continued along the course where he saw a man believed to be Mr Romero lying on the floor.
"When I got up to that point there was a lot of medical attention being given to him.
"There were about 20 Red Cross people around him.
"He didn't look good. There was a woman holding something to his neck."
The bull left runners scrambling for cover as it charged right and left.
At one point it picked a man up with its horns and flipped him into the air.
The bull kept after him as he lay curled up on the ground, covering his face.
But the man got up and ran away and was apparently not seriously hurt.
Mr Smart, a regular with the Comedy Store Players, added: "I love the sport of bull fighting. I love the adrenaline rush.
"To me it's an incredible art form to watch a man fight a bull.
"I've been doing it since 1982 so I know what I'm doing.
"But a lot of people don't realise how dangerous it is. They seem to think it's just a laugh but it's incredibly dangerous."
Fifteen people have now died at the Fiesta of San Fermin in northern Spain since record-keeping began in 1924.
This was the the first fatal goring at the event since 1995 when 22-year-old American Matthew Tassio was killed.
In 2003 63-year-old Pamplona native Fermin Etxeberri died after he was trampled on the head.
Speaking after today's incident, herder Humberto Miguel said: "It was a light bull. Its charges were not particularly strong but it moved very fast from left to right.
"Of the whole pack, it was the one that gave us the most trouble."
The six bulls used today came from a ranch called Jandilla and have a fierce reputation.
They hold the record for the most gorings in a single run - eight on a day in 2004.
The animals tend to keep running if they stay in a pack but incidents can occur if one gets separated and frightened.
The festival was made famous by writer Ernest Hemingway in his novel The Sun Also Rises.
It attracts thousands of foreign tourists each year, with many choosing to take part.
Mr Smart was injured himself in 1985 when a bull tossed him 12ft in the air, breaking two of his ribs and bruising his kidneys.
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