Shane Borthwick, vice-president of operations, said it was a "terrible day" for the company, adding that the decision has jeopardized the firm's future.
"We've brought money and talent to this province, provided a strong, sustainable sea farming model, and are now facing the most serious threat to the viability of our business at the hands of the government that invited us here in the first place," he said in a statement.
The province's minister of fisheries and aquaculture, Sterling Belliveau, said Fisheries and Oceans Canada expressed concern about the salmon farm's impact on wild salmon in the bay near Sheet Harbour during the 22-month review process.
The federal department said the site would represent a moderate risk to wild salmon. The province said it is the first time Fisheries and Oceans has described a proposed fish farm as representing a moderate risk to wild salmon.
Belliveau said the province's decision is not a sign that the government is changing its support for fish farms, which was part of its aquaculture strategy released last year.
He said the government believes the aquaculture industry can help rural Nova Scotia's economy.
"We are growing aquaculture into an economically, environmentally and socially sustainable industry, creating year-round jobs and increased wealth in rural Nova Scotia," he said in a statement.
Snow Island criticized the government's handling of the application, saying the decision was unexpected and did not appear to be based on science.
President Alan Balfour said the firm's Scottish parent company, Loch Duart, would have to assess whether to maintain operations in the province.
There has been opposition to fish farms around Nova Scotia, including proposals by Snow Island Salmon to develop farms in Spry Harbour, Shoal Bay and Beaver Harbour on the province's Eastern Shore.
Several groups have asked for a moratorium until a full environmental assessment can be done on open-pen farming to determine its impact on wild salmon, the lobster fishery and residents.
The Association for the Preservation of the Eastern Shore said rejecting the Shoal Bay proposal was the right decision for area residents.
Marike Finlay, the association's president, said she hoped future proposals would also be denied.
"It is time for Nova Scotia to get out of this destructive, dirty business and begin to invest in the future," she said in a statement.