A Melbourne police officer is fighting for her life after sustaining burns to 90 per cent of her body in an explosion during a house call at Middle Park last night.

Another female officer is in a critical condition after the blast, while a male officer and two firefighters sustained serious injuries.

The explosion occurred as emergency services were checking on a man at his Hambleton Street unit about 9:00pm (AEDT) after he had threatened to self-harm.

Police say the "offender", who is aged in his mid-to-late thirties and was inside the unit at the time of the blast, also needed treatment for burns and is now under police guard in hospital.

"Upon arrival, the firefighters gained entry to the second-floor flat and as the police entered a large explosion occurred," Victoria Police said in a statement.

A crime scene has been established and investigators are yet to identify exactly what caused the blast.

"It's early days yet. We've got a crime scene on site... and a number of members from crime command," Acting Assistant Commissioner Doug Fryer said.

"We've got a significant contingent of investigators here who will start piecing together what happened."

Firefighters use a hose to cool the burns suffered by one of the six people injured in the blast.

Mr Fryer said police have "extreme concern" for the welfare of the three officers injured in the explosion.

"One of those members is in a life-threatening condition and our prayers are with that member and their family and their colleagues," Mr Fryer said.

"This is part of the danger of law enforcement. Most days everyone gets home, but unfortunately we've had a tragedy."

One witness, Tony, says seeing the officers so badly burnt was very disturbing.

"When I got down there there was two people obviously in extreme pain on the ground being hosed," he said.

"The female was the one that was in the most pain, obviously screaming in agony.

"They were obviously badly burnt being hosed with fire hoses."

Another witness who lives near the unit described the blast, saying: "It was a big explosion and we heard a lot of glass shattering on the ground."

Mr Fryer says the firefighters' injuries are "not as severe".

"We have two members of the Melbourne Fire Brigade that have been injured, but not in a life-threatening way," he said.

"There could have been injuries to other people - thankfully there was not. Only those inside the room.

"We have an offender who also sustained injuries, which I don't believe to be life threatening."

Police said the blast caused "extensive damage" to the room, but was contained to the flat itself.

They are urging anybody with information to call Crime Stoppers on 1800 333 000.