During the 1470s, the personal musical chapel of Galeazzo Maria Sforza in Milan evolved a unique genre of motet cycles, the Motetti missales. Duke Galeazzo apparently preferred hearing his splendid choir sing motets than listening to a priest's words during the Mass. Evidence suggests that other late medieval centers allowed their musicians the more liturgically appropriate leeway to substitute simple chordal settings of devotional texts into the Sanctus of the Mass, at the most holy moment of the Elevation of the Host. Pierre de la Rue seems to have written his simple yet elegant O salutaris hostia, setting a free text in honor of the Blessed Sacrament, for such substitutionary use in the Burgundian chapel of his patrons. Three Hapsburg-Burgundian manuscript sources place this motet in place of the first text "Osanna" in the Sanctus of his Missa De Sancta Anna. O salutaris shares that Mass' clear F modality, yet interrupts the Mass' contrapuntal vigor with reflective chordal homophony, in syllabic phrases generally leading to fermata-marked cadences. Some subtle imitation glimmers through the texture, but only in the final exhortation to God for strength in the hour of death does the musical language broaden to include cascading melismas which embolden the final cadence.

Though most appropriate for the veneration of the Host during Mass, the motet perhaps knew other uses: two other manuscripts present it as a freestanding piece of devotional music. One, the so-called "Occo Codex," contains five settings of this text alone.

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