The state-run Sunday Mail quoted Mugabe as saying the opposition worked with outsiders to undermine the embattled country's sovereignty.
"There is no room for unity with those that do not believe that this country and its forests, animals, even snakes and mosquitoes belong to us," Mugabe told the paper.
"Those who work hand in glove with the enemy to impose sanctions on our country and those who are sponsored by the enemy to subvert our national sovereignty ... are indeed the enemies of this unity," he added.
The 80-year-old leader accused the opposition Movement for Democratic Change (MDC), which poses the biggest threat to his 24-year hold on power, of being a front for Western countries bent on overthrowing his government.
Earlier this year Mugabe said in an interview to mark his 80th birthday that his party would not hold talks with the MDC unless they were seen to sever their alleged links with the West.
The political temperature in Zimbabwe has been rising ahead of next year's parliamentary elections, as the ruling Zimbabwe African National Union Patriotic Front (ZANU-PF) claimed a victory in an MDC stronghold after a low voter turnout.
Last week Mugabe threatened to put the opposition to "eternal sleep" in polls due in March next year, while MDC leader Morgan Tsvangirai warned of the "chaos that awaits the nation in 2005" - Sapa-AFP.
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