Already brought to its knees by spiraling debt and huge unemployment, Spain can ill afford to lose the main contributor to its economy.
Yet that is the potential outcome of elections in the northeastern region of Catalonia on Sunday, where the separatist movement has gained ground as the economic crisis in Spain deepened.
With a population of some 7.5 million, Catalonia is Spain's second most populous region.
It generates about 19 percent of Spain's economic output and gross domestic product (GDP) per capita that is higher than the European Union average. The region has its own language and a strong cultural identity.
And as Spain slides ever deeper into recession, Catalonia wants out.
The latest polls show the separatist party, led by Artur Mas, is unlikely to win an absolute majority on Sunday, but analysts believe that a referendum on independence will nevertheless take place, most likely in the spring of 2013.
Mas argues that Catalonia would be better off on its own, even though the region recently sought emergency cash from the central government.
Like many Spanish regions, it overspent during the property boom. But Mas said the region gives more to the central government than it gets back.
"Mas had no qualms about bringing up Catalonia's economic strength even while asking for a bailout from the central government — 'Well, it's our money anyway,' " David Lea, analyst for Western Europe at Control Risks, told CNBC.com.
Even if Artur Mas' Convergence and Union party wins the 62 seats it has now — less than the 68 required to gain a majority — the outcome should not be interpreted as a defeat for separatism, Lea said.
"The two big national parties, the PP and PSOE, are struggling, particularly the latter, and look like getting fewer than 40 seats between them, compared with nearly 50 last time round, and even that was a historic low. The votes seem to be going to the nationalist left, particularly the ERC, which favors independence," he said.
He added: "Mas will have enough seats in a fragmented parliament to govern comfortably in a minority, and there will be enough outside support for him to take his independence agenda forward."
A referendum might not be "D-Day," but it could set the wheels in motion for a move towards full-blown federalism in Spain.
The road to independence would likely be long and the process drawn out, but any perception of political instability and economic uncertainty would add to Spain's troubles.
"Catalonia currently throws a major shadow over central government and growing nationalist sentiment is sending a negative message abroad about the premier's inability to keep his country united when it needs it the most," analysts at IHS Global Insight said .
Ben May, European economist at Capital Economics warned that a dramatic increase in expectations of Catalonia leaving Spain could hurt the country even more.
"Catalonia is a net contributor to that central pot of money," he said, adding it would leave Spain in a weaker position.
A victory for the separatists could rattle investors' nerves and prompt a rise in the country's borrowing costs.
A significant majority for the separatist party will further complicate the ability of the Spanish government to reign in regional budget deficits, analysts at Barclays said on Friday.
And the fallout of the Catalan election could spread well beyond Spain too.
The prospect of regional independence for wealthy regions like Catalonia — but also the prosperous northern region of Flanders in Belgium and Scotland seeking independence from Britain — bodes ill for the future of the wider euro zone, May said.
"If rich parts of individual countries try to leave because they don't want to support their poorer relations, that doesn't bode well for richer countries providing fiscal transfers (to poorer euro zone countries)," he said. "That will be a key part of the euro zone's future."
—By CNBC's Antonia van de Velde