Individual vs. Society
The central action in One Flew Over the Cuckoo's Nest revolves around McMurphy's battle against the stringent regulations imposed by Nurse Ratched. Her hospital ward functions as a micro-society with its own set of rules and penalties, affecting both the patients and the staff. From the moment McMurphy arrives, he defies these rules, whether by disrupting the "democratic" group therapy sessions or brushing his teeth outside the designated time. Through McMurphy's defiance of Nurse Ratched's absurd and oppressive rules, Kesey illustrates the individual's struggle against a conformist society as a significant and noble endeavor. McMurphy's resistance within the confines of the hospital can be seen as a metaphor for the broader societal context. During the period Kesey wrote the novel, conformity was heavily emphasized as a means to maintain law and order. By depicting one man's meaningful fight against a small society, Kesey challenges the societal norms of his time.

Sanity and Insanity
One of society's benchmarks forms the most pervasive theme in the book: What defines sanity and insanity? Is sanity simply adherence to societal norms, or is it an independent sense of self distinct from society? These questions have puzzled psychiatrists for over a century. Should their role be to recondition individuals to better fit into potentially unsatisfactory lives or flawed societies? Or is their duty to guide individuals toward self-realization, regardless of how that diverges from the norms of their environment?

By depicting McMurphy's experiences on the Acute/Chronic Ward, Kesey questions societal definitions of sanity, which seem to demand uniform behavior from everyone. When McMurphy learns that many of the Acutes are at the hospital by choice, he asks why: "You, you're not exactly the everyday man on the street, but you're not nuts." Billy Bibbit responds that they lack the "guts" to cope with life outside, but ironically, Nurse Ratched's methods are designed to erode the men's confidence rather than build it. Kesey thus portrays society's definition of "madness" as a tool used by authoritarian forces to dehumanize individuals, turning them into automatons living in safe, blind conformity. McMurphy, the hero, is the one who sees through this façade. By teaching his fellow patients to define their own sanity, McMurphy helps them reclaim their humanity from institutionalization. In doing so, he endures great suffering and ultimately sacrifices his life.

Sacrifice
McMurphy's battle against Nurse Ratched, though ultimately unsuccessful, is depicted as a sacrifice that frees his fellow patients. At the novel's conclusion, Scanlon urges Chief Bromden to escape, reminding him that McMurphy "showed you how one time, if you think back." This theme of sacrifice is further emphasized through recurring crucifixion imagery throughout the story. Consider the tragic figure of the mentally shattered Chronic Ellis, who is "nailed" to the wall in Chief's perspective, behind which ominous wires and machinery hum. Additionally, there is the cross-shaped table used for electroshock therapy. This crucifixion imagery is echoed in Chief's account of Sefelt's position during an epileptic seizure: "His hands are nailed out to each side with the palms up and the fingers jerking open and shut, just the way I've watched men jerk at the Shock Shop strapped to the crossed table, smoke curling up out of the palms from the current."

One Flew Over the Cuckoo's Nest is a prototypical 1960s novel in its strong antiestablishment stance. Presenting an archetypal conflict between Good and Evil, Kesey pits the individual against the Combine, a mechanistic, monolithic bureaucracy, whose chief representative is the Big Nurse. In the microcosm of the psychiatric ward, control is the objective — an ominous control that supplants freedom with regulations, favors monotonous routine over spontaneity, and rewards assertions of personal opinion with visits to the "Shock Shop." Dehumanization results, as the men on the ward lose their sense of self-worth and become mere robots for the Combine. One of Kesey's central concerns is the danger of conformity, of mindless capitulation to a system. Therefore, as the novel progresses, he reveals that the Combine controls not only the hospital, but American society as well, as seen in Chief Bromden's vision of 5,000 children, dressed exactly alike, who live in 5,000 houses, "punched out identical by a machine," owned by 5,000 men, who disembark from a commuter train "like a hatch of identical insects."

To combat the threat of the Combine comes the champion of nonconformity, the restorer of humanity to the men on the ward, Randle Patrick McMurphy. A quintessential American hero, McMurphy is associated with freedom, self-reliance, and nature. He encourages the men to make choices, such as voting whether to watch the World Series on television, he helps them escape the stifling routine through basketball practice and a clandestine party, and he brings them back in touch with nature by leading a deep-sea fishing trip — all the while forging the bonds of camaraderie. Kesey's prescription for mental health seems to be an oxymoronic coupling of rugged individualism and esprit de corps.

While the principal conflict in One Flew Over the Cuckoo's Nest is between the individual and the Combine, or, as some critics have expressed it, between Nature and the Machine, there is a significant secondary opposition between male and female. Kesey has conceived of the hospital environment as a matriarchy, with the reins of power in the hands of Big Nurse, who, in turn, has derived her power from a female supervisor. Nurse Ratched is an emasculator, completely subjugating the weak-spirited Dr. Spivey and transforming the men on the ward into little boys through her motherly treatment of them. She is, as McMurphy succinctly notes, "a ball-cutter." Other similarly castrating women include the white mother of Chief Bromden, Billy Bibbit's mother, and Dale Harding's wife. To restore the men's self-confidence, McMurphy, whose animalistic lust is insatiable, must first restore their sexual potency. This he does by spinning tales of young virgins that cause the Chief to have an erection and by arranging for Billy to spend a night with the prostitute Candy. He also sexually defies Nurse Ratched, from his parading before her in his whale-decorated undershorts, to his symbolic penetration of her glass-enclosed office, to his climactic mock-rape of her during which he exposes her breasts. A number of critics have objected to the novel's sexual stereotyping, especially to Kesey's association of women with repressive forces; however, other critics and Kesey himself defend One Flew Over the Cuckoo's Nest. They contend that it advocates an uninhibited expression of sexual vitality for both males and females, and that it criticizes not women per se but rather a lack of warmth and compassion.

A minor but important theme found in the novel is the oppression of minorities in America by the white power structure. Kesey expresses concern about the mistreatment of Indians through Chief Bromden's memories of how the government seized his tribe's land to build a hydroelectric dam. He also highlights Native Americans' problems with alcoholism because of cultural disfranchisement. In addition, Kesey is sensitive to the plight of blacks. Although his characterizations of the black orderlies who sodomize and humiliate the patients are morally repulsive, Kesey reveals that the lack of employment opportunities to advance from merely cleaning and scrubbing floors has made these men abusive. Furthermore, the history he provides of one black attendant who as a five year old witnessed whites rape his mother and torture his father explains why the blacks harbor intense hatred of the whites. Kesey's message is that cruelty breeds racism.