Background: Vitiligo has a significant effect on patients’ quality of life; they feel stigmatized and disturbed by their condition. A lot of vitiligo patients, according to reports, suffer from psychological disturbances. The aim of the study is to find the relation between vitiligo and stress, anxiety, and depression and to measure how vitiligo affects the quality-of-life index. Methods of study is a case-control involving fifty patients of both sexes with the diagnosis of vitiligo and fifty healthy volunteers as a control group matched in age, gender, and academic level. Patients were selected from patients who visiting dermatology clinic at King Abdul-Aziz hospital in Makkah Al-Mokarramah. All patients were assessed by the Depression Anxiety Stress Scale (DASS) to determine the severity of anxiety, depression, and stress symptoms and the Dermatology Life Quality Index (DLQI) scale to evaluate their quality of life while the control group underwent only the Depression Anxiety Stress Scale. Results: The prevalence of stress was 76%, anxiety was 78%, and depression was 80%; the difference was statistically significant between patient group and control group regarding stress, anxiety, and depression. Gender had a significant relationship with stress, anxiety, and depression (p < 0.05) (female affected more than male). Also, there was a statistically significant relation between the degree of vitiligo and anxiety (p < 0.05). Vitiligo has a moderate to very severe effect on the quality of life index. There was a statistically significant positive correlation between stress and feeling of embarrassment from vitiligo and clothes choice. Conclusion: Vitiligo is a psych cutaneous disease that does not only affect the patient’s physical status, but also his mental and psychological status.