The words of the Trisagion (which means three-time holy) come from Isaiah chapter 6, where Isaiah is brought before the throne of God, and called to be His prophet. During this encounter, Isaiah saw and heard seraphim around the throne of God who said to one another, "Holy, holy, holy is the Lord of hosts; The whole earth is full of His glory!" After hearing this, a seraph put hot coal in the mouth of Isaiah, which purged his sin. This hot coal is the body of Christ who is the Word of God, who purges our sins. Just as Isaiah heard "Holy, Holy, Holy" before receiving the Word of God in the form of coal, we sing "Holy Holy Holy" before we receive the written Word of God in the Gospel.

Similarly, just as there is a Trisagion in the Liturgy of the Word, there is a Trisagion in the Liturgy of the Faithful. This is prayed by the congregation and the priest shortly before the bread and wine become the body and blood of Christ (This change cannot be described as it is a mystery). Again, just as Isaiah heard this hymn before receiving the Word of God, we pray this before we receive the actual Word of God on the altar.