In Sweet Bird of Youth, the theme of sex and its consequences profoundly affects almost every character. After failing to make it as an actor, Chance turns to a "career" as a gigolo, providing sexual services and companionship to affluent, solitary, often older women. He meets Princess Kosmonopolis while working at a resort in Palm Beach. Due to Chance's numerous liaisons, he unknowingly passes a venereal disease to his girlfriend, Heavenly Finley, during their last meeting. Unaware of her infection, Heavenly neglects treatment, resulting in a hysterectomy. This event robs her of both her youth and her ability to have children. As a result, everyone wants Chance to leave town, either for his own protection or as a form of retribution. He refuses to go, and the play suggests that he will be castrated by the end.

For some characters, sex is closely linked to power and wealth. Princess Kosmonopolis forces Chance into a sexual encounter at the end of Act 1, Scene 1. During this scene, she is infatuated with him, and he tries to take advantage by demanding she signs some traveler's checks for him. She consents only after the encounter. Similarly, Boss Finley maintains a mistress, Miss Lucy, at the hotel. When he learns she has remarked that he is too old for sex, he seeks revenge. He offers her a diamond clip in a jewelry box but cruelly snaps it shut on her fingers when she opens it, causing injury, and then reclaims the gift. The theme of sex propels much of the play's action, both overtly and subtly.

Many characters in Sweet Bird of Youth are obsessed with the passage of time and the inevitability of aging. Despite being twenty-nine and having thinning hair, Chance still possesses enough charm to attract women like the Princess. However, the only woman he truly longs for is Heavenly, with whom he started a relationship when she was fifteen. Multiple characters remind him that she has changed, particularly due to the sexually transmitted disease he gave her, which led to her having a hysterectomy. At one point, Heavenly tells her father, "Scudder’s knife cut the youth out of my body, made me an old childless woman. Dry, cold, empty, like an old woman."

Nevertheless, Chance clings to the belief that if he can take Heavenly away, nothing will have changed; they will move to Hollywood, and he will finally find success as an actor. Heavenly represents his lost youth and the potential he once held. When Chance and Heavenly finally meet, they find themselves unable to communicate. Despite this, Chance holds onto his last shred of hope and submits to what is suggested to be castration at the end of the play.

Princess Kosmonopolis shares Chance’s fear of aging. In reality, she is Alexandra del Lago, a middle-aged actress who knows Hollywood favors youth. She does not want to retire but fled the premiere of her latest film after seeing herself on screen. The Princess hides her true identity, turning to alcohol and hashish to dull her pain. Chance serves as a comforting distraction, though she is fully aware of his intentions.

At the play's end, when Chance makes a desperate request for her to help him and Heavenly by informing a Hollywood gossip columnist about their potential as actors, the Princess discovers that not everything is lost. Her film turns out to be a success, and she is praised for making a comeback. She does not mention Chance and Heavenly. Although the Princess understands that her triumph over time is temporary and that Hollywood will eventually dismiss her due to...