Officials cautioned that they did not know how many people were in the Kleen Energy plant, which was still being built, and therefore they could not immediately account for everyone who may have been present.
"We know that 12 individuals have been injured. Five individuals are known to have lost their lives," Sebastian Giuliano, the mayor of Middletown, Connecticut, told a news conference Sunday.
Terrorism has been ruled out, according to the mayor, who said the accident, which broke the windows of nearby residential buildings and shook houses miles (kilometers) away, happened during a testing procedure.
Rescue workers helped by search dogs scoured the rubble at the plant where a brief, but fierce fire following the accident sent flames and black smoke billowing skyward.
"There was like a fireball going up and a lot of smoke. The explosion was strong enough to break one of our windows. Our neighbors had also their windows destroyed," said Scott Harmann, 44, whose father lives in a house just across the Connecticut River from the plant.
Nearby resident Mike Woronoff said he heard "a loud boom" at his house some two miles ( 3.2 kilometers) from the plant.
"I have friends that live 15 miles from here that called me because they could hear it. Then we could see the smoke. It went on for a mile and a half, then stopped," he said.
Amid confusion over the number of casualties local officials immediately warned of the potential for carnage.
"There was a massive explosion, there are multiple injuries and possible fatalities," Middletown police spokesman George Yepes told AFP soon after the blast.
"The reports vary from a few to possibly as many as 50 dead," Brian Albert from the Middlesex hospital, which was treating several of those injured, said in the immediate aftermath.
Uncertainty as to the final toll seemed set to continue until contractors working on the site are able to compile an accurate roster of those present.
A Middletown fire official said it was "initially thought there was approximately 50 employees" there at the time and that "it's unknown how many people are missing."
Giuliano said "there could be anywhere from 100 to 200 people working on the site on any given day. Exactly what's that number, that's the starting point and that's the number they can't nail down today.
"Fortunately what I was told is that most of the people working there were evacuated from the building when they ran the test," he said.
A local resident told the Hartford Courant newspaper that the explosion took place during a test of the plant's power generating systems.
The 620-megawatt Kleen Energy plant, said to be one of the largest power facilities to be planned in New England for many years, was still under construction.
The future gas-fired energy production plant is located on the outskirts of Middletown, close to residential housing.
A company called Energy Investors Funds recently acquired 80 percent of the plant, which had been due to go online sometime in 2010.
The American Red Cross said it had set up a phone number -- (860) 347-2577 -- for "anyone concerned for the well-being of a relative or a friend that was working at the Kleen Energy plant."
In Washington, Secretary of Labor Hilda Solis said inspectors from the Occupational Safety and Health Administration had arrived on site to conduct a comprehensive investigation.
"The safety and health of workers is of paramount importance to me and to the US Department of Labor," Solis assured.
The US Chemical Safety Board (CSB) said it would send a seven-person team to the blast site. The team is expected on the scene midday Monday, the independent investigative agency said in a statement.
"The CSB's investigative team will examine the activities that were ongoing at the time of this accident, including any gas purging, as indicated by initial media reports," lead investigator Don Holmstrom added.