A Saudi soldier was shot dead patrolling an area populated by minority Shi'ite Muslims late on Friday, the Interior Ministry said, and one of the gunmen was killed in the ensuing shoot-out.
The deaths bring to 11 the number of people killed in the Qatif area since November in protests by members of Saudi Arabia's Shi'ite minority over what they see as entrenched discrimination.
"A security patrol was exposed to heavy fire from four armed rioters on motorbikes when pausing at a street intersection in Qatif," state news agency SPA reported, quoting Interior Ministry spokesman Mansour Turki.
Turki said the gunmen had been arrested after an exchange of fire in which one of them was killed, and said another man suffering a bullet injury had been arrested at the hospital.
He added that the incident, which happened at 11 pm on Friday evening, had led to the death of one soldier, named as Hussein Bawah Ali Zabani, and the wounding of another, named as Saad Miteb Mohammed al-Shammari, whom he said was taken to hospital.
Saudi Shi'ites mostly live in the Eastern Province, also home to the kingdom's oil industry, and complain they lack access to government jobs, education and full rights of worship, charges the government denies.
The world's top oil exporter follows the conservative Wahhabi school of Islam, which regards Shi'ism as heretical.
Protests broke out in Qatif last year when Saudi troops were invited by the government of neighboring Bahrain to help its Sunni royal family quash a popular uprising by the Shi'ite majority.
Last month a new round of protests ended with three deaths after police arrested and injured a firebrand Shi'ite cleric, Nimr al-Nimr, who had preached sermons urging demonstrations against the government.
Ten of the 11 people to have died in Qatif demonstrations since late last year were young Shi'ite men, killed in what Saudi Arabia said were exchanges of fire, but which local activists described as peaceful protests.
Saudi Arabia and Bahrain have both accused Shi'ite regional power Iran of fomenting the unrest among members of the sect in both countries, which Tehran denies.
The Interior Ministry in January issued a list of 23 residents of the area who it said were responsible for attacks on security forces, acting at the behest of "a foreign power", widely understood to mean Iran.
Shi'ites in Qatif, who often raise the Bahraini flag in shows of solidarity with their co-religionists in the tiny Gulf Arab country, have repeatedly said the protests are not organized by Iran.