Independence could expose Scotland to an environmental disaster, according to new research.
A study of tree rings has uncovered a famine that decimated the country more than 300 years ago.
Caused by an extremely cold period in the 1690s, it destroyed farming and wiped out up to 15 percent of the population.
It even sparked a fatal attempt to establish a colony in southern Panama.
It was not just bad weather to blame. Scotland was politically isolated from England, its bigger and more prosperous neighbour that might have otherwise helped.
The catastrophe was one of the reasons the two nations merged in 1707 to become part of what is now the United Kingdom.
Such a tragedy was never repeated - despite later climate swings, say the US team.
As Boris Johnson 'Gets Brexit Done' the researchers think Nicola Sturgeon and other politicians need to heed the lesson.
Lead author Professor Rosanne D'Arrigo, a tree-ring scientist at Columbia University in New York, explained: "'By joining England, Scotland became more resilient.
"The bigger message for today is arguably that as the climate changes, nations will be stronger if they stick together and not try to go it alone."
England had more good farmland and, at the time, better agricultural technology and organisation for delivering relief to the poor.
While also hit with cool weather, England did not suffer a famine, and probably would have come to the aid of Scotland had the nations been united.
Scotland also unwisely encouraged the export of crops at a time when they were needed at home.
Co-author Dr Rob Wilson, an environmental scientist at St Andrews University, said: "Scotland became more resilient when it became part of a union. It's a cautionary tale from history."
At the height of the crisis, the Scots developed an intricate venture to send colonists to the Darien region of Panama.
Driven by desperation, the idea caught on and people of all social and economic classes invested much of their assets - as much as half the nation's entire liquid capital.
Starting in 1698, a total of 2,500 colonists began sailing to this malarial jungle coast. They were quickly cut down by disease, malnutrition and conflicts with Spanish forces, which already controlled much of South and Central America.
The colony was abandoned after just 16 months; only a few hundred colonists survived - and Scotland was financially ruined. The inhospitable Darien region remains barely inhabited even today.
Prof D'Arrigo said: "At the time, the Scots saw the colony as a kind of Exodus, where they would start over somewhere new. In the end, they couldn't escape."
The study published in the Journal of Volcanology and Geothermal Research showed the end of the 17th century was Scotland's coldest decade of the past 750 years.
Based on the width and density of old tree rings they collected, the researchers found it was probably triggered by volcanic eruptions in the tropics.
During the 'Scottish Ills' - named after the biblical plagues - snow persisted on the ground well into summer - when frosts struck every night for weeks.
The planting season was cut short, and crops were struck down before they could be harvested. Livestock had nothing to eat.
The study quotes Mary Caithness, Countess of Breadalbane, describing "cold misty weather such as the oldest person alive hath not seen."
France, England and the Netherlands also suffered - but generally with less drastic results. In Scandinavia tens of thousands died.
It was "likely the worst era of crop failure, food shortage and mortality ever documented in Scottish history," the researchers write.
At the time much of the northern hemisphere was already in the grip of the Little Ice Age when cold temperatures were the norm for centuries - until the 1800s.
Dr Wilson said: "Before this, we knew it was cold. Now we have an understanding of exactly how cold.
"The whole 17th century must have been a horrible time to live in Scotland - but this was the worst part."
The findings are part of the Scottish Pine Project in which his team have been gathering tree-rings for the past 10 years in northern Scotland.
Samples range from the desolate Highlands dating back to the 1400s to the bottom of the icy lochs - some of which are 8,000 years old.
The researchers are still collecting samples and working to construct a continuous climate record predating the Middle Ages.
Scots re-considering independence to rejoin the EU and leave the isolationist English to fend for themselves need to think twice, said the researchers.