Background: This study aimed to investigate the relationship between personal and clinical characteristics of adults in the Tehran Lipid and Glucose Study (TLGS) with depression, anxiety, and stress. Methods: Data of 2272 adults participating in the 6th phase of TLGS were used for univariate analysis to investigate the association between socio-demographic, behavioral, and clinical characteristics and participants’ emotional states. Thereupon, the predictors with a P value<0.20, at least for one of depression, anxiety, and stress in the primary analysis, were included in the model for multivariate modeling. Results: The mean age of participants was 47.23±14.87. The mean scores of depression, anxiety, and stress were higher in women (P value:<0.001,<0.001, and 0.004) than in men. Higher age was associated with lower anxiety (β=-0.04, P=0.004) and stress (β=-0.13, P<0.001) in men, but only lower stress in women (β=-0.07, P=0.001). Highly educated participants experienced lower depression (β=-2.26, P=0.01, β=-2.26, P=0.003). Although married men robustly experienced lower depression than others (β=-1.69, P=0.009), a less powerful relationship existed between being married and depression in women (β=-1.37, P=0.05). All cigarette smokers experienced higher depression, anxiety, and stress, but only female hookah smokers had higher anxiety and stress. Physical activity and chronic disorders had no relationship with emotional states. Obesity was associated with stress in women (β=1.95, P=0.001). Conclusion: This study provides an update on factors associated with mental health outcomes in a large general population. Examining the factors associated with depression, anxiety, and stress through a sex-sensitive lens could help clinicians diagnose and plan the best preventive and therapeutic approach.