The Spanish government has declared the vote illegal and police have seized ballot boxes. Spain's prime minister Mariano has insisted the referendum “won't happen”.
There is strong support for independence among Catalonia's 7.5m population – including from Manchester City boss Pep Guardiola - but parties loyal to Spain are boycotting the vote.
Among the many uncertainties is what will happen to the region's football clubs, including FC Barcelona, if Catalonia becomes a new country.
Gerard Figueras, Catalonia's minster of sport, said: “In the case of independence, Catalan teams in La Liga – Barcelona, Espanyol and Girona – will have to decide where they want to play: in the Spanish league or a neighbouring country: Italy, France or the Premier League.
“Now in Spain there teams from other countries who play in national leagues: clubs from Andorra in football and basketball. Monaco play in France, in England Welsh clubs. I don't think that UEFA has anything against seeing another club play in a different league from their country.”
Spain have insisted Barcelona will not be allowed to play in La Liga if the illegal vote goes through.
La Liga president Javier Tebas said: “In sport, it isn't a la carte and things must be clearly stated. It isn't easy to have an agreement and study Spanish legislation but if they (Catalan clubs) do get that, then they will not be able to play in Spain's La Liga, but I hope it doesn't come to that."
Guardiola, who has played for Catalonia's representative side, has backed independence. Speaking at a rally in June, the Manchester City manager said: “We have no other option but to vote. We call on the international community to support us and on democrats the world over to help us to defend the rights that are threatened in Catalunya, such as the right of freedom of expression and the right to vote.”
A recent statement from Barcelona said: “FC Barcelona, in holding the utmost respect for its diverse body of members, will continue to support the will of the majority of Catalan people, and will do so in a civil, peaceful, and exemplary way.”