Background: Chronic spontaneous urticaria (CSU) is common, chronic, and debilitating, and has serious effects on quality of life and mental health. Three of 4 patients with CSU are women. The impact of CSU on female sexual functioning remains largely unknown. Objective: To determine the prevalence of sexual dysfunction in female patients with CSU and to characterize their impairment of sexual functioning and its drivers. Methods: Fifty-six female patients with CSU and 55 female aged-matched healthy control subjects were evaluated for sexual functioning with the Female Sexual Function Index. Patients were also assessed for their duration, activity, and control of disease, as well as angioedema, anxiety, depression, fatigue, and quality-of-life impairment. Results: Sexual functioning, that is, total Female Sexual Function Index scores and all subscores, was markedly reduced in female patients with CSU versus control subjects, and 2 of 3 patients (67.9%) had sexual dysfunction. Impaired sexual functioning was linked to high disease activity and poor disease control. Sexual dysfunction was more common in patients with CSU with angioedema and vice versa. Angioedema was a significant predictor of sexual dysfunction in female patients with CSU (odds ratio, 7.3). Reduced sexual functioning was associated with anxiety, depression, and fatigue and significantly linked to impaired quality of life, more so in patients with angioedema as compared with those without. Conclusions: CSU has strong negative effects on female sexual function, especially in patients with angioedema. Additional studies on sexual health in patients with CSU are needed and should focus on the impact of effective treatment on sexual functioning.