Josep Maria Jove, the secretary general of economic affairs and number two to the region's vice president Oriol Junqueras, was arrested on Wednesday morning by Spain's Civil Guard.
Thousands of people protesting the arrest in Barcelona were demonstrating in front of the Catalan Ministry of Economy on Wednesday morning.
The Public Diplomacy Council of Catalonia quoted Junqueras as saying "They (the civil guard) are entering everywhere. We're encountering a state which acts without warrants."
The Council later announced the arrests of "12 high-ranking officials" of the Catalan government and searches of their premises.
Artur Mas, former president of Catalonia, in March was given a two-year ban on holding public office for organizing a referendum in 2014, deemed illegal under Spanish law.
The central government is waging myriad legal battles to halt the October 1 referendum called by the regional parliament in Catalonia in northeastern Spain.
Spain's Constitutional Court had suspended the referendum law passed by the regional parliament earlier this month.
The referendum comes six days after the Kurdistan Region in northern Iraq is scheduled to hold its own referendum on independence. The central government in Baghdad has also deemed Kurdistan's referendum to be "illegal" and empowered Iraq's prime minister to take steps to prevent the vote.
At the behest of PM Haider al-Abadi the Iraqi Supreme Court filed a court case against Kurdish President Masoud Barzani and parliament Speaker Yousif Mohammed.
Abadi's office has also stated that Kurdistan's referendum will lead to "dangerous consequences."
The Kurdish parliament voted on Friday to back the referendum at its stated time for Monday.
Last updated at 1:30 p.m.
