Themes of Largo Desolato include isolation, political upheaval, and staying true to yourself.

The theme of political upheaval provides the backdrop for the entire play. Something that Nettles has written has attracted negative attention from the government. Knowing this makes him paranoid because he fears that he will be taken away. Nettles' family and friends are also worried about either him being taken away or him refusing to stand up for his beliefs.

Isolation is another theme in the play. In the first two scenes, Nettles is alone on the stage. He's paranoid and nervous. When Edward finally enters, Nettles says he just feels better if someone is there. However, his situation isolates him emotionally from the people around him. He's increasingly unable to write and feels pressured to change his views and actions by those around him.

Ultimately, however, the theme of being true to yourself takes center stage. When the government agents return to arrest Professor Nettles, he says that they can take him away because he will not give up authorship of his works. He says, "I’d rather die than give up my own human identity—it’s the only thing I’ve got." He would rather be imprisoned than say he didn't write "Ontology of the Human Self." After he's stated his decision, he's informed that his case has actually been adjourned indefinitely—for the time being. While this might bring others joy, it actually distresses Nettles, who can't stand the idea of more uncertainty and isolation.