The speaker addresses a female persona, probably the titular "Tirzah," to ask what business he has with her. He starts by pointing out that he is mortal and will die ("be consumed with the Earth") and rise again, so he asks what he could have to share with the woman. He declares that the sexes originated from "Shame & Pride" and lived only to "work & weep." He then addresses the "Mother of [his] Mortal part" who has cruelly shaped his heart and through deceit bound his "nostrils Eyes & Ears" and silenced his "Tongue in senseless clay." He declares that the death of Jesus has set him free (from sin, perhaps) so again, "what have I to do with thee?"
The title of this poem references Song of Solomon 6:4: “My darling, you are as beautiful as Tirzah, as lovely as Jerusalem, as awe-inspiring as bannered armies!” Besides referring to a magnificent city of Solomon’s day, Tirzah actually means “beauty” or “pleasure.” Thus, Blake directs the poem to an image of physical beauty and pleasure, the female evocation of sexual desire in him.
When he begins the poem, however, Blake references his earthly mother, the giver of his physical form. He asks her “what have I to do with thee?” since anything born of mortal flesh “must be consumed with the Earth.” In the second stanza he takes up the theme of sexuality, stating that the sexes “sprung from Shame & Pride,” possibly referencing Adam’s sin and the subsequent shame felt by both him and Eve in Genesis 3. God’s mercy changed the penalty of death for Adam’s disobedience “into Sleep,” the temporary end of mortal life before the general resurrection of all the dead as foretold in the New Testament. However, the “Mother of my Mortal part,” his human body, still makes his life miserable by binding his “Nostrils Eyes & Ears” with “self-deceiving tears.” He feels betrayed to “Mortal Life” by his mother, but finds comfort that “The Death of Jesus set me free.” However, he still ends with the refrain, “Then what have I to do with thee?” Neither sexuality nor maternal care can bring him to a state of eternal life; only the sacrifice of Jesus Christ is capable of making him whole once more. As Blake included in his engraving for this poem, once his physical body dies, “It is raised a Spiritual Body,” as stated in I Corinthians 15:44.