Objectives: Studies have reported a higher risk for obstructive sleep apnea (OSA) in major depressive disorder (MDD). However, the risk of OSA in patients with chronic treatment-resistant depressive symptoms is not well documented worldwide. Hence, the current study assessed the risk of OSA and associated factors in patients with chronic treatment resistant depression (cTRD). Methods: The study recruited 140 Iranian patients with cTRD. All patients completed the Berlin questionnaire, which evaluates the risk of OSA. Additionally, demographic data and history of cardiovascular or metabolic diseases were collected. Pearson's Chi-square test, Fisher's exact test, and independent T-test were used to assess group differences, when appropriate. Results: The study found that 89 of 140 cTRD patients (64%) were at high risk for OSA. Group comparison between cTRD patients (high vs. low risk for OSA) demonstrated that at high risk OSA-cTRD patients had an elevated rate of hypertension, diabetes mellitus, and obesity. Also, age, duration of depression, and duration of treatment were significantly higher in cTRD patients with higher risk compared to those with lower risk for OSA. Conclusions:The results suggest that a noticeable number of patients with cTRD are at high risk for OSA, which is higher than the reported magnitude in the general population. Moreover, hypertension, diabetes mellitus, and obesity are associated with a higher risk for OSA. Also, age, treatment duration, and depression duration could be considered as possible comorbid factors for OSA in patients with cTRD.