Simultaneously, Western approaches to controlling the plague are attempted,[11] but the islanders resist quarantine measures, resulting in an increasing number of infections and deaths.

[12] Matt A. Hanson of World Literature Today noted that the motifs of Nights of Plague are prevalent in the latter years of Ottoman collapse, notably during Abdul Hamid II's disastrous reign.

Pamuk fictionalizes the formation of the fragmented political identities that sparked World War I and eventually strengthened the foundations of the Turkish republic.

[13] In The Atlantic, Judith Shulevitz wrote that Nights of Plague is plainly satire and metaphor, mordantly riffing on Ottoman, revolutionary, and nationalist leadership styles in a critique of Atatürk, Kemalism, and even President Erdoğan's government—but not in a single sentence.

[6] In his review for The Times, Peter Kemp wrote that Nights of Plague masterfully weaves a tale of intrigue and disease.