The Red Cross has appealed to both sides to allow civilians to leave the combat zone.
Thousands of civilians are reported to have gathered in a 35 square kilometre area declared a safe zone by the army, but human rights groups are reporting that the area has been shelled.
"When the dust settles, we may see countless victims and a terrible humanitarian situation unless civilians are protected and international humanitarian law is respected in all circumstances," de Maio said.
Pranab Mukherjee, India's foreign minister, echoed that concern in an emergency meeting with Mahinda Rajapakse , Sri Lanka's president, on Wednesday.
Mukherjee called on the government to take urgent measures to protect civilians caught up in fighting.
The United Nations has issued similar warnings, with Ban Ki-moon, the UN secretary general, saying he was "deeply concerned" for the safety of civilians caught in the fighting.
'Zero civilian casualties'
Sri Lanka's government insists there have been "zero civilian casualties" in its operation to crush fighters from the Liberation Tigers of Tamil Eelam (LTTE) in their last remaining bastion in Mullaittivu district.
But doctors on the ground say this is far from the case.
"Three dead bodies of civilians were brought in on Tuesday and 15 more admitted injured due to the heavy shelling," T Satyamurthy, the director of Udaiyaarkaddu hospital, was quoted by the AFP news agency as saying.
Most of Mullaittivu district is now under government control following the military's offensive.
Tony Birtley, Al Jazeera's correspondent who visited Mullaitivu under the oversight of the army, said that the LTTE, who are fighting for the creation of an independent Tamil state in northern Sri Lanka, appears to have fled the town.
He said the town was largely empty, with most civilian residents apparently retreating with the Tamil Tigers.
The government has said civilians are being forced to move with the Tigers to act as human shields, but there has been no independent confirmation of that.
In an interview with Al Jazeera, Gotabaya Rajapaksa, the Sri Lankan defence minister, said that government forces exercised extreme caution during the offensive and only fired on Tamil Tiger rebels.
He dismissed the claims of civilian deaths as LTTE propaganda, insisting that no civilians have died in the recent fighting, and that reports to the contrary should not be believed.
"We don't use indirect fire unless we are 100 per cent certain that those are LTTE camps or bases ... This is all LTTE propaganda," Rajapaksa said.
The official death toll is unknown as medical officials have said they have been ordered by the health ministry in Colombo not to reveal casualty figures.
No journalists are allowed into combat zones in Sri Lanka on their own.