In a TV interview, he warned that US President Donald Trump would leave the White House “stained with blood” if he intervened in the crisis.
He also defiantly rejected the EU’s Sunday deadline to call snap elections.
Opposition leader Juan Guaidó declared himself interim president last month and won US backing.
He said on Sunday he would build an international coalition to deliver humanitarian aid to Venezuelans but Mr Maduro has accused him of organising a coup.
In the interview with Spanish television programme Salvados, broadcast on Sunday, Mr Maduro was asked if the crisis in Venezuela could result in civil war.
“Today no-one could answer that question with certainty,” he said.
“Everything depends on the level of madness and aggressiveness of the northern empire [the US] and its Western allies.
“We ask that nobody intervenes in our internal affairs… and we prepare ourselves to defend our country.”
President Trump has told US broadcaster CBS the use of military force remains “an option”.
But Mr Maduro warned the US leader he risked a repeat of the Vietnam War if he intervened.