The illness of Sultan Mahmud II, the 30th Sultan of the Ottoman Empire and the 109th Islamic Caliph, started to be discussed after his death. In this study, the possible illnesses of Sultan Mahmud II, his illness process and death were analysed by comparing the claims and explanations made by his physicians during his illness and death. The research includes: the incomplete document of Abdülhak Molla, the chief physician of the period; the book titled Deux Annees de l’Histoire d’Orient 1839-1840 (Two Years in the East 1839-1840) written by Edmond De Cadalvene and Emile Barrault; the book titled Relation Officielle de la Maladie et de la Mort du Sultan Mahmud II (Sultan Mahmud II’s Illness and Death) by Mac Carthy and Konstantin Kara Todori. The Illness and Death of Sultan Mahmud II), published in 1841; and, three reports sent by Karl Ambros Bernard to the Austrian government on different dates based on Jakob Neuner. In the light of current medical knowledge, the above-mentioned information and documents about the sultan’s illness suggest that Sultan Mahmud II suffered from “lung cancer” and “alcohol withdrawal syndrome”. It was concluded that his death was due to sepsis developing as a result of the infection caused by the disease and the deterioration of metabolite balances in the body.