More than half of Northern Ireland's exports went to the EU last year, economic data said.
The trade was worth £3 billion, according to Revenue and Customs.
Northern Ireland director of the CBI Angela McGowan said businesses were seeking the freest possible trade between the UK and EU.
"However, ruling out membership of the single market has reduced options for maintaining barrier-free and tariff-free trading relationship between the UK and the EU.
"Given the importance of the EU to NI exports, the significance of leaving the single market is an important issue for the local economy.
"While local businesses want to make a success of Brexit, there are undoubtedly concerns about falling back on damaging World Trade Organisation (WTO) rules."
The business lobby group welcomed the Prime Minister's commitment to maintaining the "family ties and bonds of affection between the UK and the Republic of Ireland" and the Common Travel Area.
Ms McGowan added: "Close co-operation and partnership between the two countries will be essential if the Northern Ireland economy is to succeed."