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Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disease often associated with non-atopic comorbidities. Recently, a severity-dependent relationship between AD and sleep/mental health diseases has been proposed. However, few studies investigated these comorbidities and their association with AD severity through validated questionnaires. This study aimed to use a set of validated instruments to assess the impact of AD on sleep and psychological disorders and estimate the association of itch and AD severity with sleep disorders and psychological symptoms, distinguishing between clinical-oriented and patient-oriented measures. Methods: We conducted a case-control study, recruiting 57 adult AD patients (mean age ± std. dev. 34.28 years ± 13.07; 27 males) matched for age and sex with 57 healthy adults (34.39 years ± 13.09; 27 males). To investigate the differences in sleep quality, insomnia, depression, and anxiety between the two groups, we performed independent sample t-Tests. Moreover, we conducted univariate linear regression analyses to examine the relationship between itch and objective/subjective severity of AD and sleep quality, insomnia, and psychological symptoms. Results: AD patients reported lower sleep quality (p = 0.002), more severe insomnia (p = 0.006) and depression (p = 0.013), and higher stress levels than healthy adults (p = 0.049). Itch intensity was linked to sleep disturbances and psychological symptoms (R2range = 0.13–0.19, prange = 0.02–<0.001). Objective and subjective AD severity were similarly associated with worse sleep quality (R2 = 0.26, p < 0.001; R2 = 0.24, p < 0.001; respectively), anxiety (R2 = 0.15, p = 0.04; R2 = 0.17, p = 0.001; respectively), and self-perceived stress (R2 = 0.10, p = 0.02; R2 = 0.07, p = 0.049; respectively). However, subjective AD severity was more strongly associated with insomnia (R2 = 0.31, p < 0.001) and depression (R2 = 0.20, p < 0.001) than clinical-oriented AD severity (R2 = 0.19, p < 0.001; R2 = 0.05, p = 0.098; respectively). Conclusions: The study demonstrated poor sleep quality and high levels of insomnia, depression, and stress in AD patients, with an aggravated psychological status for adults with more severe skin disease. We suggest implementing a multidisciplinary approach to AD management/treatment that considers objective and subjective measures of disease severity. [ABSTRACT FROM AUTHOR]