In a speech in London, the prime minister will argue that the whole UK would be "deeply diminished" if Scotland opted to leave.
Mr Cameron will also warn supporters of the Union against "complacency".
But the Scottish National Party said he was "cowardly" for not making the speech in Scotland.
Mr Cameron will invoke the spirit of the Great Britain Olympic team, which won 65 medals in 2012, when he speaks at the Olympic Park in east London.
He will say: "For me, the best thing about the Olympics wasn't the winning. It was the red, the white, the blue.
"It was the summer that patriotism came out of the shadows and into the sun, everyone cheering as one for Team GB."
About four million people over the age of 16 and living in Scotland will be able to take part in the referendum, promised by the country's ruling Scottish National Party, on 18 September.
Mr Cameron will say: "This is a decision that is squarely and solely for those in Scotland to make. I passionately believe it is in their interests to stay in the UK.
"That way Scotland has the space to take decisions, while still having the security that comes with being part of something bigger."
Scotland is "part of a major global player", the prime minister will say, adding that, although only four million people can vote in the referendum, "all 63 million of us are profoundly affected".
"That's why this speech is addressed not to the people of Scotland, but to the people of England, Wales and Northern Ireland. We would be deeply diminished without Scotland," he will say.
"This matters to all our futures. And everyone in the UK can have a voice in this debate."
The UK is "a powerful brand" and Scottish independence would "rip the rug from under our own reputation", he will say.
Mr Cameron will also say: "The plain fact is we matter more in the world together. There can be no complacency about the result of this referendum. The outcome is still up in the air."
He will urge people in England, Wales and Northern Ireland to "let the message ring out" that: "We want you to stay."
But Scotland's Deputy First Minister, Nicola Sturgeon, said: "This is a cowardly speech from a prime minister who uses the Olympic Park in London to give high-handed lectures against Scotland's independence but hasn't got the guts to come to Scotland or anywhere else to make his case in a head-to-head debate.
"David Cameron, as the Tory prime minister, is the very embodiment of the democratic case for a Yes vote for an independent Scotland - and he knows it."
She added that "using the Olympic stadium on the day the Winter Olympics begin and seeking to invoke the successes of London 2012 as an argument against Scotland taking its future into its own hands, it betrays the extent of the jitters now running through the No campaign.
"They see the polls closing and they are clearly rattled - but to politicise any sporting occasion is shameful."
Labour MP and supporter of the Union, Tessa Jowell, defended Mr Cameron's use of the Olympic Park for his speech, saying the venue helped to remind people how "we felt to be British".
Asked whether that was a feeling only among the English, she told BBC Radio 4's Today: "When the Olympic torch went through Scotland, Wales and Northern Ireland, there was a sense of the UK being together, being proud of our British identity.
"We saw modern Britain and what it means to be British in the 21st Century over that summer in the Olympic Park."
From BEN Latest News: www.benlatestnews.com
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