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Background Sestrins (Sesns) family, which including three members Sesn1, Sesn2 and Sesn3, is known as stress-inducible proteins and participate in multiple diseases via regulating oxidative stress, inflammatory response and cell apoptosis. The present study aimed to investigate the plasma levels and the clinical significance of Sesns in patients with coronary artery disease (CAD). Methods In the case-control study, 119 CAD patients, including stable angina pectoris (SAP, n = 44), unstable angina pectoris (UAP, n = 41) and acute myocardial infarction (AMI, n = 29) were included. Patients with chest pain syndrome but excluded CAD (n = 35) were enrolled as control. Plasma levels of Sesn1, Sesn2, Sesn3, superoxide dismutase (SOD) and malondialdehyde (MDA) in all patients were measured and analyzed. Results Compared with control group, plasma levels of Sesn1, Sesn2 and Sesn3 were significantly increased in patients with SAP, UAP and AMI. In addition, a significant lower SOD levels and higher MDA levels were observed in CAD patients, Sesn1/2/3 levels were negatively correlated with SOD levels and positively correlated with MDA levels. Gensini Score were positively correlated with Sesn1/2/3 levels and MDA levels, whereas negatively correlated with SOD levels. Furthermore, as the main risk factors for CAD, the elderly and obesity increased plasma Sesn2 levels, diabetes increased both plasma Sesn2 and Sesn3 levels. Conclusions Our study was the first to report that the plasma Sesns levels were increased in CAD patients and positively related to the severity of coronary heart disease. Although the exact mechanisms of Sesns in CAD are still unknown, alleviated oxidative stress may be the possible reasons. [ABSTRACT FROM AUTHOR]