The groups report said that Scotlands net deficit would be large and volatile, forcing the new government to maintain austerity at a similar pace to the rest of the UK.
John Cridland, CBI Director-General, said: The minute you draw a line between Gretna and Berwick, Scotland starts to drift apart from its biggest market and loses a significant amount of economic clout.
The CBIs report added that a new border would create additional costs for businesses and consumers, including the cost of complying with new cross-border tax rules.
Cridland added: Scotlands economy is a real success story as part of the UK it has the independence and flexibility of devolution alongside the support of the union.
The fate of Scotland is, of course, a decision for the Scottish people, but business is clear – we are stronger together.
The CBIs intervention is unsurprising opposition to Scottish independence is common throughout the UKs business community but there are business voices within Scotland which see merit in the idea.
Entrepreneur Tony Banks, chairman of campaign group Business for Scotland, said that the CBI had got it wrong by failing to address several issues in the Scottish Governments independence whitepaper including plans to expand immigration, cut business taxes and increase the number of women on boards.
He said: The CBIs argument on the question of Scotlands membership of the EU simply parrots the UK Governments position with nothing about the threat of a UK referendum on EU membership.
“The CBI offers nothing at all on how to rebalance the economy to the nations and regions outside London, how to boost growth and productivity, how to expand exports and address inequality in the interests of prosperity for all.