Background: The association between life-event stressors and low physical activity linked to the severity of coronary artery disease (CAD) is poorly understood. Therefore, this study aimed to determine the perceived stress status and physical activity level associated with the severity of CAD. Methods: The study was conducted among 423 patients with newly discovered CAD (both sexes, aged 35–65 years) confirmed by coronary angiography results. CAD severity was classified according to the Gensini score as severe or non-severe. The fasting blood glucose and lipid profiles were also investigated. Anthropometric and brachial blood pressure measurements were obtained. A structured questionnaire including participants’ characteristics, the Perceived Stress Scale (PSS-14), and the International Physical Activity Questionnaire were used via face-to-face interviews. Multivariable binary logistic regression was used to assess the predictors of CAD severity using IBM SPSS ver. 24.0 (IBM Corp., Armonk, NY, USA). Results: Most participants were classified as having severe CAD (63.8%). Adjusting for age, sex, smoking status, systolic blood pressure, body mass index, and history of hypertension, the severity of CAD increased by 9% for a onescore increase in the PSS (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.01–1.14; P=0.030). Moreover, sufficiently active (600–1,500 metabolic equivalents [METs]/wk) patients had lower odds of severe CAD (OR, 0.43; 95% CI, 0.23–0.72; P=0.027) than those with insufficient activity. However, no significant association was found between physical activity (≥1,500 METs/wk) and CAD severity. Conclusion The odds of CAD severity significantly increased with increasing perceived stress score but decreased with sufficient physical activity.