The annual Fiesta de San Fermin, made famous by the 1926 novel of USA writer Ernest Hemmingway entitled "The Sun Also Rises", involves the daily running of the bulls through the historic heart of Pamplona to the bull ring.
The man, a 46-year-old from the United States, was speared by a bull's horn in the city's bull ring, at the end of the 850-metre course.
National media outlets noted that some people have so far suffered serious injuries, including a 23-year old man from Florence whose name was not released.
The festival, which draws thousands of people around the world, kicked off on Saturday in Pamplona in northern Spain with pomp and gaiety.
Two others were taken to hospital with head injuries and a total of 48 others were treated by the Red Cross.
One of several bull running fiestas held around Spain every year, San Fermin was made famous when it featured in US author Ernest Hemingway's novel "The Sun Also Rises".
Since the festival began in 1910, 15 people have been killed in the run, majority due to being gored.
Zion to miss rest of Summer League after knock
Jackson played with extreme poise and showed his leadership abilities when he led the team on a 20 to 7 run right before halftime. The past and future of the New Orleans Pelicans embraced prior to Zion Williamson's first exhibition game as a professional.
The festival was immortalised in American novelist Ernest Hemingway's 1926 book, "The Sun Also Rises".
Sunday morning's inaugural run featured bulls from the Puerto de San Lorenzo cattle breeder, which also caused one goring previous year.
One of them stumbled toward the end, causing panic and at least one goring when it charged at some racers.
Three people were rushed to hospital this morning at the start of the Running of the Bulls in Pamplona, northern Spain.
Red Cross officials said in an initial injury round-up that two people had been taken to hospital with gore injuries.
On top of the race and endless partying, the festival also includes music performances, traditional sports and dance displays, a religious procession on Sunday and a firework competition.
Cebada Gago ranch, which is known for raising ferocious beasts had sent six bulls for the run on Sunday.