Background: Depression is an important issue in asthma. Uncover depression in asthmatic patients has important implications for identifying patients and suitable treatment of these patients this will improve quality of life, decrease medication intake and decrease hospitalization. Objective: The aim of this study was to determine the prevalence of depression among adult asthmatic patients in Jizan region, Saudi Arabia. Patients and methods: Cross-sectional study that was conducted in Jizan region at the chest diseases hospital. 270 (18-90 yrs.) asthmatic patients were recruited. The questionnaire including socio-demographic data, clinical risk factors of asthma, assessment of asthma by using asthma control test (ACT) and assessment of depression by using Patient Health Questionnaire-9 (PHQ-9). Results: Out of 270 adult asthmatic patients, 255 responded (94.4%). The mean age of patients was 41.03 ± 15.893 years. The prevalence of depression among adult asthmatic patients was 32.9%. By multivariate analysis the lower education level [elementary school or below (Odds ratio 3.219 (95% CI; 1.443-7.177)] and longer asthma duration (22 years and above) Odds ratio 2.065 (95% CI; 1.089-3.916) were independently associated with the development of depression in adult patients with asthma. Conclusion: The study showed that there was a high prevalence of depression among adult asthmatic patients in Jizan region, Saudi Arabia. The higher prevalence of depression was associated with lower education level, longer asthma duration, poor control of asthma and among married subjects. Screening for depression in adult asthmatic patients should be emphasized in primary health care centers, chest clinics and in hospitals. Adult asthmatic patients should be motivated to comply with asthma treatment.