Background: Myocardial infarction (MI) is a major cause of death worldwide. Several acute-phase inflammatory proteins such as interleukin-6 (IL-6) and C-reactive protein (CRP) have been examined as the potential indicators of atherosclerosis and the risk of coronary artery disease (CAD). This study aimed to examine whether inflammation could explain the relationship between depression and CAD. Methods: In this repeated-measure cross-sectional study, we measured CRP and IL-6 in 162 patients with acute MI at the time of admission and on the fifth day. The patients were categorized into depressed and non-depressed groups based on the Beck Depression Inventory questionnaire. Additionally, on the fifth day of hospitalization, a checklist of acute MI complications was completed for each patient. Results: The depressed patients had a significantly higher mean value of IL-6 and CRP than the non- depressed group (for IL-6, F=17.06 and P<0.001; for CRP, F=8.92 and P=0.002). Moreover, the depressed patients experienced more post-MI brady- and tachyarrhythmias. Conclusions: The depressed patients with acute MI had a higher level of inflammatory factors and more complications such as arrhythmias in their hospitalization period, which might have affected their prognosis. Therefore, it is imperative that more attention be paid to CAD patients with depressed mood in terms of the management and assessment of their prognosis. (Iranian heart Journal 2018; 19(3): 20- 29)