It was something Pope Benedict warned about on his state visit to Britain last year.
Cardinal O'Brien will say the enemies of Christianity want to "take God from the public sphere".
The cardinal has made a reputation for his robust defence of traditionalist Christian teaching.
But BBC religious affairs correspondent Robert Pigott says even by Cardinal O'Brien's standards his Easter sermon constitutes a vehement and outspoken attack on secularism and what he will describe as the enemies of the Christian faith in Britain and the power they currently exert.Equality legislation
He will call on Christians of all denominations to resist the efforts of such people to destroy Christian heritage and culture.
In a reference to equality legislation preventing discrimination against homosexual people, Cardinal O'Brien will denounce what he claims is the way Christians have been prevented from acting in accordance with their beliefs because they refuse to endorse such lifestyles.
Cardinal O'Brien will remind his congregation at St Mary's Cathedral in Edinburgh of the plea by the Pope that Christians of different denominations should rediscover their common ancestry to unite in resisting the sidelining of religion.
The Anglican archbishops of Canterbury and York, Dr Rowan Williams and Dr John Sentamu, are also due to deliver Easter messages on Sunday.
The Catholic archbishop of Westminster, the Most Reverend Vincent Nichols, will speak of his hopes for peace in conflict-hit countries such as Libya, Syria, Afghanistan and Ivory Coast.
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