The blaze was under control, but the exact number of fatalities remained unknown, said Jose Turcios, spokesman for the Comayagua, Honduras, fire department.
Some 35 prisoners were transported to a local hospital, he said, and some were then taken to a hospital in the capital.
Five of the prison's units -- more than half of the prison -- were affected by the fire, Turcios said. The prison holds 851 prisoners.
The cause of the blaze is under investigation, he said.
The country's prison commissioner said authorities are looking into whether a short circuit sparked the fire or if possibly a prisoner set a mattress on fire.
The blaze broke out at 11 p.m. Tuesday (12 a.m. Wednesday ET).
Before dawn Wednesday, families of the prisoners were already gathering in front of the prison gates and officials' offices, demanding to know if their loved ones were among the survivors.
The fire was the third fatal prison fire in recent years. In 2003, 61 prisoners were killed in a fire at a prison in La Ceiba. In 2004, the death toll was 107 from a fire in a San Pedro Sula prison.
TheU.S. State Departmentpublished a report last April which painted a damning portrait of conditions in Honduras' 24 prisons.
Prisoners "suffered from severe overcrowding, malnutrition, and lack of adequate sanitation," it cited human rights groups as saying.
"Authorities did not provide adequate food or other basic necessities. The ready access of prisoners to weapons and other contraband, impunity for inmate attacks against nonviolent prisoners, inmate escapes, and threats by inmates and their associates outside prisons against prison officials and their families contributed to an unstable and dangerous penitentiary system environment," the department said in its 2010 Country Reports on Human Rights Practices.
Human rights groups also alleged that prison officials used excessive force against prisoners, theState Department said.
As of December 2010, the total prison population in the country was just under 12,000, about 400 of whom were women, the report said.