The theme of sexuality is subtly woven throughout the story. Hickock struggles with monogamy, resulting in two marriages and two divorces. While in Mexico, he becomes engaged twice and even has an intimate encounter with one fiancée while Smith is present. Hickock's hidden sexual deviance involves an attraction to young, sometimes prepubescent, girls. Smith has to stop Hickock from assaulting Nancy Clutter in her home, and later reveals his disdain for individuals who "can't control themselves sexually." There are hints suggesting Smith might be homosexual, and his contempt for casual sexual behavior could stem from his own struggles to manage and conceal his sexual identity.

Hickock, who openly expresses homophobia, calls Smith "baby," "sugar," and "honey," and eventually decides he wants to separate from Smith due to his constant complaining. In the Army, Smith often drew the attention of homosexuals and was initially reluctant to befriend Willie Jay because he seemed overly delicate. Smith believed that Hickock complemented him well, describing him as "totally masculine." While Hickock constantly attempts to prove his heterosexuality to Smith, Smith, in turn, showcases his potential for violence to Hickock. This dynamic is fueled by each man's insecurity about his own sexuality.