The Catalan regional government confirmed Josep Maria Jove, secretary general of economic affairs, was among those arrested.
On Wednesday, Spain attempted to stop the independence vote from taking place, followed by Spain's finance minister Cristóbal Montoro declaring that they were now set to take control of a large part of Catalonia's public finances.
Spanish police have also raided print shops and newspaper offices in a hunt for voting papers, ballot boxes and leaflets, while Catalonia's top court has warned newspapers not to publish campaign notices for the referendum. It gave no details on the number of agents involved.
It's all kicking off in Catalonia, the northeastern region of Spain that's preparing for a referendum on its independence at the start of October.
A man holds pro-referendum posters in Catalan in front of the Economy headquarters of Catalonia's regional government in Barcelona on September 20, 2019, during a search by Spain's Guardia Civil police.
Asked whether the vote could prove as divisive as the Brexit referendum has in the United Kingdom, the Catalan government source replied: "Democracy doesn't divide; it's the absence of democracy that divides people..."
Carles Puigdemont appeared with members of his cabinet Wednesday following several arrests in an ongoing operation by Civil Guard agents. So far, an estimated 700 Catalan municipalities have said they will offer their public buildings, such as schools, to be used as polling centers on October 1.
This vote has been declared illegal by the Spanish Constitutional Court, which has instructed both Spanish and Catalan regional police to do everything possible to stop it being held.
The measure means that virtually all the Catalan public spending will be in the hands of Madrid.
Catalonia represents a fifth of Spain's 1.1-trillion-euro economy.
Following Wednesday's morning raids, key figures in the region's independence movement took to Twitter.
He added: "This is a judicial operation which is being done to guarantee ... that the law is respected".
"People seem to be ignoring it, strangely", said Nick Henderson, a sales trader at Spanish brokerage Ahorro Corp.in Madrid.
Thousands of pro-independence protesters took to the streets of Barcelona in the wake of the latest developments, with one group blocking the path of a vehicle belonging to the Spanish police, Guardia Civil. Both officials declined to be identified by name, following internal protocol.
Chants in support of independence are also common at the Camp Nou in the 17th minute to mark the fall of Catalonia in the Spanish War of Succession in 1714.