Atopic dermatitis (AD) is a chronic inflammatory skin disease presenting as xerosis, eczema and intense pruritus. These symptoms negatively impact patients’ quality of life. However, the effect of AD on sexual function and sleep quality and how treatment with dupilumab could modify them have not been explored in depth. The aim of this study is to assess the effects of dupilumab on sexual and sleep quality in patients with AD. For that purpose, an observational prospective study was designed. Patients were evaluated at baseline and after 16 weeks of dupilumab treatment. Disease severity was assessed by Eczema Area and Severity (EASI) and SCORing Atopic Dermatitis index (SCORAD). Sexual function was evaluated using validated questionnaires, for men via the International Index of Erectile Dysfunction 5 (IIEF-5) and for women via the Female Sexual Function Index (FSFI). Sleep impairment was recorded through Pittsburgh Sleep Quality Index (PSQI). Thirty-two patients, with a mean age of 30.53 ± 14.48 years old, were included. Regarding sex, 59.8% (20) were female. Most patients had a severe disease reflected in a mean basal EASI of 23.24 ± 6.74 and a SCORAD of 54.07 ± 13.89. Clinical scores improved after dupilumab treatment. At baseline, 47.37% women presented sexual dysfunction and 66.67% men had erectile dysfunction. FSFI improved from 23.51 to 27.93 points (p = 0.008) after dupilumab. Desire, arousal, satisfaction and pain were the components with great improvement. Women with a great improvement in FSFI showed greater clinical results and increased quality of life. At first, 96.9% (31/32) of participants presented with poor sleep quality. After treatment with dupilumab, sleep quality was enhanced and PSQI scores decreased from 12.8 points at baseline to 7.73 points (p < 0.001). In conclusion, dupilumab is associated with reduced sexual dysfunction, mainly in women, and sleep quality.