The Holy See's secretary of state, Cardinal Pietro Parolin, said he was saddened by the vote which saw 62% of Irish voters backing same sex marriage.
"I don't think you can speak only about a defeat for Christian principles, but a defeat for humanity," he said.
The Catholic Church in Ireland has already admitted it needs a "reality check" after the poll.
Archbishop of Dublin, Diarmuid Martin, said the vote was part of a "social revolution" and he feared the Church had "drifted completely away from young people".
Pope Francis also appears to have commented on the vote.
Whilst not directly referring to Ireland's referendum the Holy Father used his weekly general audience yesterday to stress traditional church teaching on marriage as being between man and woman.