The incident came two weeks after unrest at a state-run shelter for children resulted in a fire that killed 40 girls.
The National Civil Police confirmed that two monitors were dead at the Central Correctional Stage II prison in San Jose Pinula, about 12 miles (20 kilometers) east of the capital.
Officials said inmates also started a fire in part of the prison, and police threw tear gas canisters seeking to regain control.
Volunteer firefighters told local media that the monitors who were killed had been beaten, but the cause of death had not been determined.
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