The prevalence of depression among the general population has been estimated as up to 50% and even higher among asthmatics. The aim of this cross-sectional study was to evaluate the prevalence of depressed mood among asthma patients (n = 280) attending a pulmonary clinic in Tehran and compare it with measures of severity of asthma and of health and well-being. The prevalence of depression symptoms on the 28-item general health questionnaire (GHQ-28) was 65.4%. Patients’ individual scores on the GHQ-28 were significantly correlated with the number of asthma medications used, frequency of visits to the pulmonary clinic and frequency of hospitalizations for asthma, but not with FEV1. A significant correlation was found between patients’ total scores on the GHQ-28 and total and subscale scores on the Saint George respiratory questionnaire. The GHQ-28 may be useful for screening for asthma patients who need more attention and therapeutic intervention for psychiatric disorders.