The number of UK service personnel killed as a result of the Afghanistan conflict since 2001 has hit 300, after a wounded marine died in hospital.
The MoD said the man, from 40 Commando Royal Marines, died in Birmingham's New Queen Elizabeth Hospital on Sunday. His family has been informed.
He had been injured in a blast in the Sangin district of Helmand on 12 June.
The prime minister said it was a moment for the whole country to reflect on the sacrifices the armed forces make.
David Cameron said the marine's death was "desperately sad news" and another family was suffering "grief, pain and loss".
"The 300th death is no more or less tragic than the 299 that came before," he said.
"But it's a moment for the whole country to reflect on the incredible service and sacrifice and dedication that the armed forces give on our behalf."
About 10,000 British military personnel are in Afghanistan as part of a 45-nation Nato-led force.
It was deployed in the wake of al-Qaeda's 9/11 attacks on the US, with the aim of unseating Afghanistan's then Taliban rulers said to be harbouring those responsible.
Mr Cameron, who recently warned the UK to expect more casualties during the summer of this "vital year", acknowledged that many people questioned the country's role.
"We are there because the Afghans are not yet ready to keep their own country safe and to keep terrorists and terrorist training camps out of their country."
UK forces would withdraw as soon as Afghanistan could ensure its own security, he added.
Afghan President Hamid Karzai's spokesman said he recognised the forces' sacrifices "to bring peace and stability to Afghanistan, to the region and to the rest of the world".
It was nearly seven years before the UK's dead in Afghanistan numbered 100 but the past two years have seen an increasing casualty rate.
Last year was particularly bloody, largely because of the proliferation of insurgents' increasingly sophisticated roadside bombs, with the 200th death marked in August and more than 100 over the calendar year.
It has taken just 10 months for the total to increase to 300, with about 4,000 British troops involved in Operation Moshtarak, aimed at shoring up government control in southern Helmand.
British military spokesman Maj Gen Gordon Messenger said the threat of makeshift bombs, known as IEDs, was a daily part of life for troops.
"The threat is getting more lethal in that the IEDs - that is the weapon of choice - are widespread on the ground. We are also on patrol more," he said.
Troops were operating "in areas that would be of no surprise to the Taliban" to deliver security to the population, he added.
Some 34 of the 300 deaths have been from accidents, illness or non-combat injuries.
Another 1,282 UK military and civilian personnel have been wounded in action since 2006, including about 388 who suffered serious or life-threatening injuries. Of those, 120 lost limbs.
The Ministry of Defence has no clear record of how many casualties there were before then, although statistics show 10 were seriously hurt.
Speaking about the latest death, 40 Commando spokesman Maj Renny Bulmer said: "Our thoughts are with his immediate family who were with him at the hospital.
"His courage and sacrifice will not be forgotten."
The death was announced as it emerged three Australian commandos and a US soldier had been killed in a helicopter crash in Kandahar province. Seven other Australians were injured, two seriously.
The US has suffered the most fatalities of the coalition partners, losing 1,125 personnel since 2001 according to the independent iCasualties website, although its presence numbers 100,000.
However, countries with much smaller military force in the country have suffered significant losses.
For example Denmark, whose presence numbers 750, has suffered 33 fatalities, while 147 Canadian personnel have died from its force of about 2,800.
The chief of the defence staff, Air Chief Marshal Sir Jock Stirrup, said personnel from across the world were "putting their lives on the line" every day and that people owed them their backing.
Defence Secretary Liam Fox said the UK's resolve to see through the mission and prevent the creation of a "security vacuum" in Afghanistan remained "steadfast".
The British deputy commander of the Nato-led force, Lt Gen Nick Parker, said individual tragedies must not be allowed to affect the mission's plan.
"What people want is definable progress so that we start to bring sustainable security to Afghanistan, and that's what we're doing," he told the BBC.
However, shadow foreign secretary David Miliband said the government must have a "clear strategy" to bring the conflict to an end.
"That can't be done by military means alone. It needs a political settlement," he added.
Meanwhile, at a protest outside Downing Street on Tuesday, the Stop the War Coalition will demand troops are withdrawn immediately.
Convenor Lindsey German said: "This is obviously a very sad occasion but... the government should now admit there is no justification for British troops to be in Afghanistan and bring them home."
Labour MP for Newport West, Paul Flynn, told the BBC it was a "complete myth" that fighting in Afghanistan could stop al-Qaeda.
"They already can work in those areas where the Taliban occupy in Afghanistan. We're only there in a small area, and they can also operate in Pakistan, and in the Gulf, and in north Africa."