The fire came at the beginning of Eid al-Adha - the holiday of the sacrifice.
The Islamic Centre of Fort Pierce had an Eid prayer scheduled for yesterday. Those who wanted to worship were instructed to go to another mosque in the area.
"It is with a very heavy heart that we have to announce that there was an arson attack on our Mosque," the Islamic Centre said. "Please keep us in your Du'as and prayers."
It's unclear how much damage was done to the mosque. But a spokesman for the Council on American-Islamic Relations Florida chapter said the "whole centre is a crime scene now."
Major David Thompson with the St Lucie County Sheriff's Office told reporters it was a "horrible tragedy not only for the Islamic centre but for our community."
"I don't want to speculate on a motive," he said. "We all know the implications of the date and the time of year that this is - the 9/11 anniversary. Is that related? I wouldn't want to speculate, but certainly that is in the back of our minds."
Thompson told reporters that "evidence has revealed that this fire was set intentionally."
The mosque became a locus of attention in June, after Mateen opened fire at a gay nightclub in Orlando, killing 49 people and leaving dozens of others injured. Mateen was killed in a shootout with police inside the Pulse nightclub.
Mateen occasionally attended the Islamic Centre of Fort Pierce, coming to prayers with his father and young son, Imam Shafiq Rahman said in June. Mateen's three sisters were active volunteers at the mosque, which has about 150 congregants.
"He was the most quiet guy - he never talked to anyone," Rahman said days after the Orlando massacre. "He would come and pray and leave."
Mateen was at the mosque just two days before the deadly shooting rampage.
The first American to carry out a suicide bombing in Syria, Moner Mohammad Abusalha, also occasionally worshiped here before he left his car outside the mosque in 2014, flew to Syria, burned his US passport and blew himself up in an operation for an al-Qaeda affiliate.
Ibrahim Hooper, national spokesman for the Council on American-Islamic Relations, said attacks against the American Muslim community are becoming a daily occurrence in America since Islamophobia moved into the mainstream.
"Unfortunately, within the past year, we've seen an unprecedented rise in bigotry in our society," he said today, adding: "It's becoming a great concern to the American Muslim community."