Background and Aim of the Study. While several studies have suggested a relationship between adverse postoperative outcomes and systemic lupus erythematosus (SLE) in major surgical settings, no study to date has explored postoperative outcomes of SLE patients undergoing coronary artery bypass grafting (CABG). This study aimed to compare the characteristics and outcomes of SLE patients compared to non-SLE patients undergoing CABG. Methods. We utilized the Nationwide Inpatient Sample (NIS) data from 2008–2018 for CABG patients ≥18 years old. Patients were divided into two groups based on SLE status (confirmed SLE diagnosis or no SLE present). Primary outcomes were in-hospital mortality, favorable discharge, and length of stay (LOS). Secondary outcomes included acute kidney injury (AKI), acute liver injury (ALI), hemodialysis, acute myocardial infarction (AMI), and cardiogenic shock. Patient characteristics including age, sex, race, and preexisting comorbidities were considered. Multivariable models, adjusting for confounding variables, were utilized. Results. Data from a total of 352,772 patients who underwent CABG were analyzed. 980 patients had a diagnosis code for SLE. SLE and non-SLE patients had similar rates of in-hospital mortality (OR = 0.92, [0.63–1.35]), nonhome discharge (OR = 1.09, [0.95–1.24]), and LOS (OR = 1.02, [0.99–1.06]). SLE patients developed AKI at a higher rate (OR = 1.50, [1.05–1.48]) and ALI at a lower rate (OR = 0.35, [0.16–0.74]). Both groups had similar rates of hemodialysis (OR = 1.19, [0.98–1.44]), AMI (OR = 0.93, [0.81–1.06]), and cardiogenic shock (OR = 0.8, [0.61–1.05]). Conclusion. These findings suggest that SLE patients undergoing CABG have similar mortality, discharge disposition, and LOS compared to non-SLE patients. However, SLE patients are at increased risk of AKI and decreased risk of ALI than non-SLE patients. These associations warrant further investigation to elucidate their physiologic basis.