Background & aimStress, anxiety, and depression are among the major public health problems worldwide. These problems, which may lead to more challenges, continue to grow. Therefore, the aim of this study was to investigate the main factors affecting the prevalence of stress, anxiety, and depression among citizens of Karaj.Materials & methodsA total of 920 people participated in the study. The Depression, Anxiety, and Stress Scale (DASS), consisting of 21 items, was used for the assessment of the studied problems. Single and multiple regressions were used for the data analysis. In addition, all statistical analysis was done by Stata version 12 at the 0.05significance level.ResultsWe found that the prevalence rate of depression, anxiety, and stress was 4.79%, 13.28%, and 15.13%, respectively. Education level was significantly associated with stress (b: 1.21; p < 0.001), anxiety (b: 2.03; p < 0.001), and depression (b: 0.48; p: 0.039). The association of the female gender with stress (b: 2.05; p < 0.001) and anxiety (b: 1.01; p: 0.002) was also confirmed. The association of being divorced or widowed with stress (b: 1.84; p: 0.005), anxiety (b: 1.21; p: 0.001), and depression (b: 1.85; p: 0.003) was approved. There was also a significant association between family size and stress (b: 0.39; p: 0.041). Gender and economic status were known as the most effective factors in the incidence of the studied problems.ConclusionThe prevalence rate of depression, stress, and anxiety in Karaj should be taken into consideration. Therefore, the preventive and therapeutic measures need to be considered for reducing the effects of the risk factors.