In the first stanza, the speaker is telling the reader not to reject melancholy or sadness. It is told negatively: "no," "not," "neither," "nor." Moreover, the first two words, "No, no," imply the speaker's forcefulness towards their opinion. The speaker also tells the reader what not to do, for example, they should not "go to Lethe," or forget their sadness, they should not commit suicide, and should not become fixated on objects of death or sadness (“the beetle,” the “death-moth,” and the “owl”). The speaker says that it will make the “anguish of the soul” drowsy, and the reader should do everything they can to stay aware of his suffering.
In the second stanza, lines 1-4 describe the physical circumstances literally and the emotional circumstances figuratively. For example the clouds are "weeping," which is an act of melancholy. Also, literally, flowers are usually positive but in line 3 they are “droop-headed” so they figuratively become negative (sadness or grief). The speaker then tells the reader/sufferer what to do in place of the things he said not to do in the first stanza. When bothered with "the melancholy fit," the sufferer should instead replace his sorrow with beauty, “glutting it on the morning rose”, "on the rainbow of the salt sand-wave," or “in the eyes of his beloved.” The last four lines turn from nature to people. For example, the mistress, while she shows her anger, she enjoys her beauty (peerless eyes).
In the third stanza, "she" refers to the mistress in stanza II and to melancholy. The speaker explains that happiness and pain are related: “Beauty must die”, “joy is fleeting”, and the “flower of pleasure is forever”, "turning to poison while the bee-mouth sips." The speaker says that the melancholy comes from inside the "temple of Delight," but that you can only see it if you fill yourself with joy until it uncovers the sadness, by "bursting Joy's grape against his palate fine." The person who can do this “shall taste the sadness" of melancholy and "be among her cloudy trophies hung.”
The speaker implies that all the good things in life, such as beauty and joy are mixed with pain and sadness. This idea is true in reality. Melancholy or sadness and pain come with all situations in life. The poem emphasizes that the more we are happy in life, the more we are subject to melancholy. The speaker believes humans must satisfy their desire for happiness in a world where happiness and pain are connected.