Although Sensei feels guilt for having caused his friend's death, he comes to believe that K's death was not a direct consequence of his unhappiness in love, but rather the same loneliness from which Sensei himself suffers. Similarly, in the view of most critics, "psychological guilt [is] less important than philosophical isolation". McClellan traces the theme of seeking relief from isolation through Soseki's earlier works of The Gate and Kojin to its solution in Sensei's suicide in Kokoro.
Although guilt comes into play, taking responsibility for one's actions and mistakes is paramount in the Confucian and Japanese ideology portrayed in the novel, and Sensei understands those traditions. Sensei clearly feels responsible for K's suicide, displayed in his constant trips to the cemetery at Zoshigaya to visit K's grave, his belief that he is being punished by heaven, or is destined for misery and loneliness, his belief that he must never be, or can never be, happy, because of this betrayal of K. Thus, as is often the case in Japanese culture (particularly in the Tokugawa era, but also certainly carried on beyond it), Sensei's suicide is an apology and an attempt to show penitence, or to do something about one's mistakes. He writes on several occasions that he has long known he must die, but has not the strength to kill himself just yet. He is constrained by weakness, and has not the strength to hold to either those traditional Japanese values, or the new modern Western ones that were fast replacing them throughout the Meiji era.
Jun Etō attributes the focus on isolation in Soseki's work to a philosophical crisis which the author underwent while studying in London. His contact with the more individualistic ideas of the West shattered his faith in the Confucian scholar-administrator model of traditional Japan, but he retained enough of his traditional upbringing to preclude a wholehearted embrace of Western thinking; leaving him, "a lonely, modern man". The fallen man of Soseki's conception could only escape through madness or suicide, or live on and continue to suffer.
Doi Takeo provides a contrasting interpretation of the novel, in which the psychological dominates and which sees Sensei's life as a descent into first madness, then suicide. Noting inconsistencies in Sensei's account of his uncle's fraud, he argues that Sensei's perception of his uncle's behaviour was a schizophrenic delusion created by changes in Sensei himself. He finds further confirmation of this assessment in Sensei's belief that he is being first persecuted, then entrapped by the family he goes to live with, and in the voice which Sensei says talked to him in the years after K's suicide. Sensei's own end he interprets as a homoerotic act, "loyally following his beloved into death".
Although Sensei's story is the climax of the novel, about half its length is devoted to the story of the narrator. Many commentators have noted the similarity between the narrator and the younger Sensei. The narrator is at an earlier stage in his own transition from a simplistic celebration of life in the opening pages to his own growing separation from mankind. The extent of the latter becomes apparent when he returns home to find that he is no longer in sympathy with his own family.
This second part of the novel, in which Sensei is physically absent, also serves as a contrast between the unthinking contentment of the narrator's father and the thoughtful discontent of Sensei. McClellan compares the "strength and dignity" of K's and Sensei's suicides with the physical indignity of the father's death, while still noting the tranquility the father manages to retain. Doi Takeo in his psychological readings sees the narrator's preference for Sensei over his real father — culminating in the abandonment of his dying father for the already dead Sensei — as a case of "father transference".
There has been much debate over the reasons for Sensei's eventual suicide. Eto Jun ascribes to it a "dual motivation": a personal desire to end his years of egoistic suffering, and a public desire to demonstrate his loyalty to the emperor. This position is supported by Sensei's own statement (albeit in jest) that his suicide would be, "through loyalty to the spirit of the Meiji era", while earlier in the book he had explicitly connected his isolation with the times he lived in: "loneliness is the price we have to pay for being born in this modern age, so full of freedom, independence, and our own egotistical selves". Isamu Fukuchi, however, contests both these points. He argues that suicide to end his own suffering would make no sense after having already endured the suffering for many years, while a distinction is to be made between loyalty to the Meiji emperor and loyalty to the spirit of the Meiji era. He sees the latter as being the conflict between, "modern ideals and traditional morality". Sensei's suicide is therefore a recognition that the end of the Meiji era has rendered as anachronisms those who, like him, are torn between modernity and tradition.