Background: Hearing loss is a highly prevalent condition in the world population that determines emotional, social, and economic costs. In recent years, it has been definitely recognized that the lack of physiological binaural hearing causes alterations in the localization of sounds and reduced speech recognition in noise and reverberation. This study aims to explore the psycho-social profile of adult workers affected by single-sided deafness (SSD), without other major medical conditions and otological symptoms, through comparison to subjects with normal hearing. Methods: This is a cross-sectional, case-control study. Subjects aged between 24 and 65 years, all currently employed and affected by SSD, were enrolled. They were administered both disease-specific and psychometric tests, such as the Hearing Handicap Inventory for Adults (HHIA), the Profile Questionnaire for Rating Communicative Performance, the Psychological General Well-Being Index (PGWBI), and the Social Functioning Questionnaire (SFQ). Results: A total of 149 subjects (mean age = 49.9; SD ± 8.5) were enrolled in the period 2021–2023; 68 were males (45.6%), and 81 were females (54.4%). The normal hearing group was composed of 95 subjects, and the SSD sample was composed of 54 subjects. The results of our study show that the levels of psychological well-being and social functioning in subjects with SSD are statistically worse than in the group of subjects with normal hearing in most subscales. Conclusions: This study definitely outlined evidence for a significantly worse psychological health status and a poorer social attitude of working adults affected by SSD with respect to their normal-hearing counterparts. Understanding the impact of SSD on patients’ work environment suggests a multidisciplinary approach to such patients in order to increase their quality of life through adequate counseling, acceptance, and role modeling.