Background: Coronary artery disease (CAD) is the most common form of heart disease and a leading cause of death worldwide. Extensive clinical and statistical studies have identified several factors that increase the risk of CAD and myocardial infarction. Aim: To investigate the relationship between severity of CAD, anxiety, depression, and health-related quality of life (HRQoL). Methods: A total of 225 patients (116 men, 109 women) who underwent elective coronary angiography were included. All patients were assessed for the presence of cardiovascular risk factors and ongoing medications. A biochemical examination of blood was performed in all patients before the procedure. The 225 patients were divided into three groups (a control group, and minimal and significant CAD groups) based on their Gensini score, which evaluates the severity of CAD. The Nottingham Health Profile (NHP) was used to measure HRQoL. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS). Results: A significant positive correlation was found between HADS and Gensini scores (HADS-anxiety: r = 0.139, p = 0.038; HADS-depression: r = 0.156, p = 0.019). A significant positive correlation was also determined between NHP-total and Gensini scores (r = 0.145, p = 0.029). According to the NHP, energy (p = 0.048) and physical mobility status (p = 0.021) were better in the control group than they were in the CAD groups. Conclusions: Our study demonstrates that anxiety, depression, and HRQoL are related to CAD severity. Therefore, emotional status and HRQoL should be evaluated during routine clinical treatment of CAD. Copyright © Polskie Towarzystwo Kardiologiczne.