Research carried out by North Wales Tourism found that 40% of businesses in the region across tourism, hospitality, retail and leisure could fold if there are any more lockdowns.
The study, conducted with support from North Wales Business Council, also revealed that 17% of those who responded said they had already made redundancies as a result of coronavirus restrictions.
More job losses are predicted to come as almost a third of the companies that took part said they were planning further redundancies by the end of March.
Ashley Rogers, the commercial director of North Wales Business Council, is calling for more financial support from Welsh Government. He said the research shows that even without more lockdowns, "we are looking at major job losses".
He warned: "Should further lockdowns restrict travel and therefore access to north Wales for our main sources of visitors, the north west of England and the Midlands, then the majority of our businesses in these sectors are unable to trade viably, even if they are allowed to remain open.
"We will not avoid the catastrophic economic and mental health fallout in these sectors if more lockdowns are brought in, without further Government support and that needs to be coordinated between UK and Welsh Government."
More than 360 companies from across north Wales took part in the Trade Impact Survey.
For the average business, only 18% of their turnover was generated by customers who live in the same county.
For places like hotels, guest houses, camping sites and caravan parks, that number is even lower.
More than two thirds of businesses said that trading is not viable for them under a local lockdown and they would need to close until travel restrictions were lifted.
Concerns were also expressed about the impact the crisis was having on the mental and physical health of people running the businesses.
Over a third said their mental health was badly affected while 13% said their physical health had suffered.
Jim Jones, the chief executive of North Wales Tourism and the chair of the Business Council, said although health must be a priority, the results of this study should act as a warning.
"We understand that public health comes first but the results of this study shout from the rooftops what is coming down the line, if further lockdowns are put in place without further support," he said.
"The private sector in our region needs two things, meaningful engagement around future lockdowns and the data that supports them and new financial support, should new restrictions be put in place."
Sara Jones, head of the Welsh Retail Consortium, said: "This survey provides a stark warning of the challenges ahead for the retail industry in north Wales.
"The extent to which retail remains the cornerstone of our high streets and can remain the largest private sector employer will be heavily dependent on the decisions made by MSs and governments.
"Government support for retail during the pandemic has been substantial, but lockdowns and travel restrictions have had a devastating impact. With retailers' revenues continuing to fall short more will be required."
A Welsh Government spokesperson said: "We recognise what a difficult and challenging time this is for business. Our £1.7 billion plus business support package means companies in Wales have access to the most generous offer of help anywhere in the UK.
"This is equivalent to 2.6% of our GVA and complements other UK Government schemes which are available."
"Following the Prime Ministers announcement last night [Saturday 31 Oct], we have had confirmation from the treasury that backdated JRS support will be provided to employees eligible on new terms from 23 October", they said.
They added that Welsh government are "continuing to explore further options for supporting businesses".
They also reminded that "businesses can still register for and benefit from the £200 million Lockdown Business Fund of ERF [Economic Resilience Fund] 3 as well as apply to other UK Government led schemes".
Another branch of the ERF fund, the Business Development Grant, has been suspended by Welsh Government while applications are processed due to "high demand".
The Prime Minister announced on Saturday 31 that the furlough scheme, due to end that day, was being extended until December 2.