The composer will be present as Pope Benedict XVI launches a Year of Faith for the Catholic Church round the world, and in his role, MacMillan will receive a symbolic copy of the Catholic Church's Message to Artists composed 50 years ago at the end of the Second Vatican Council.
The Ayrshire-born composer, a devout Catholic whose faith has inspired many of his works, will attend the Mass in St Peter's Square, joined by several hundred bishops and cardinals.
The composer said he was "proud" to have been invited to represent his fellow artists in Rome.
He added: "I have long been aware of Pope Paul's message to artists at the end of the 2nd Vatican Council. I have always found it moving.
"It shows that the Church does not discriminate. It was a message to all artists not just Catholic ones.
"In it he said 'if you are friends of genuine art, you are our friends'. This reminds us that the Church's historic mission is the same as Christ's – to the whole of mankind."
He added: "Art can be a window on to the mind of God. Through this window we can encounter beauty and divine truth.
"Artists can be peculiarly susceptible to the breath of the Holy Spirit which can then inspire their work.
Recent works by MacMillan include a mass setting for choir and congregation sung during the state visit of Pope Benedict XVI to Great Britain in 2010.
Archbishop Rino Fisichella, the head of the Vatican's Commission for a New Evangelisation, said: "At the end of the Mass, there will be a sign to indicate that the teachings of the Council retain all their validity and deserve to be better known and studied.
"This sign will mirror Pope Paul VI's consignment of Messages to the People of God in 1965."
"Those same Messages will be consigned by Pope Benedict XVI to various people – political leaders, representatives of the world of science and thought, artists, women, workers, the poor, sick and suffering, and to young people."