Luis de Guindos told Spanish radio that the turmoil has caused the region’s growth to slow down and has hit the eurozone’s fourth biggest economy as a whole.
The region’s growth accounts for around one-fifth of Spanish gross domestic product.
Growth reduced from 0.9% to 0.4% in the last quarter, the economy minister said.
He said: “Catalonia used to have growth above that of Spain, it was one of the drivers of the Spanish economy. However, in the fourth quarter, it’s become a burden.”
He added that the crisis could “easily have cost a billion euros”.
Turmoil broke out during the independence referendum in Catalonia on 1 October last year, where 2 million people defied the courts and governments and voted for independence.
The vote was ruled illegal because the regional law, known as the ‘self-determination referendum law’, was not backed by the Spanish constitution.
Spain cut its growth forecasts for 2018 in October to 2.3% instead of the 2.6% previously predicted.
Following the unrest, some 3,100 firms have moved their headquarters elsewhere.
The Spanish government dissolved the regional parliament and called a snap election last month, but it failed to provide a decisive result, with separatist groups winning 70 of 135 seats in parliament.
A pro-unity party won the most seats, while the Ciudadanos (Citizens) party won the popular vote. A government is yet to be formed.