Abstract: (1) Background: We hypothesized measuring the extent of brain overwork can extrapolate the burden of mental distress. This study aimed to develop a scale that measures mental distress and validate it in the general population. (2) Methods: In this population-based cross-sectional study, we recruited a total of 739 adults aged 16-65 years from 64 sampling centers of a clinical cohort across Mongolia to validate a 10-item self-report questionnaire. Internal consistency was measured using the McDonald’s ω. Test-retest reliability was analyzed using intraclass correlation coefficients. Construct and convergent validities were examined using the principal component analysis (PCA) and confirmatory factor analysis (CFA). Hospital Anxiety and Depression Scale (HADS) and the abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF) were used to evaluate the criterion validity. (3) Results: Among the participants, 70.9% were women, 22% held a bachelor's degree or higher, 38.8% were employed, and 66% were married. The overall McDonald’s ω coefficient was 0.861 demonstrating evidence of excellent internal consistency. The total intraclass correlation coefficient of the test-retest analysis was 0.75, indicating moderate external reliability. PCA and CFA established a three-domain structure that provided an excellent fit to the data (RMSEA=0.033, TLI=0.984, CFI=0.989, χ2=58, p=0.003). This 10-item scale, the Brain Overwork Scale (BOS-10), determines mental distress in three dimensions: Excessive Thinking, Hypersensitivity, and Restless Behavior. All items had higher item-total correlations with their corresponding domain than the other domains, and correlations between the domain scores ranged from 0.547–0.615. The BOS-10 correlated with the HADS, whereas it was inversely correlated with the WHOQOL-BREF. (4) Conclusions: The results suggest that the BOS-10 is a valid and reliable instrument for assessing mental distress in the general population. The current findings also demonstrate that the BOS-10 is quantitative, simple, and applicable for large-group testing.