Abstract Background The COVID-19 pandemic has been a worldwide challenge. In patients with coronary artery disease (CAD), previously submitted to coronary artery bypass graft surgery (CABG), such impact should be analyzed. Objectives Evaluate the impact on quality of life of COVID-19 infection in patients with prior CABG. Methods Patients undergoing isolated CABG between July 2016 and July 2017 were enrolled. This is an observational, cross-sectional, prospective study. Patients were divided into two groups: Group (COVID-19) and Group (No-COVID), for analysis of variables. The World Health Organization’s (WHO) definitions of confirmed cases were used to define the diagnosis of COVID-19 infection. Quality of life was assessed using the Quality of Life in Cardiovascular Surgery (QLCS) questionnaire, applied 30 days, 6 months, 1 year, and 4 years after surgery. The primary endpoint was improvement in quality of life at 4 years after CABG. The local ethics committee approved the study. Continuous variables were described by their means and standard deviations (SD). Categorical variables were described using absolute or relative frequencies. The items that make up the quality of life questionnaire were added together to calculate the score. A linear mixed model was used to assess the effect of time on the score. The significance level adopted was 5%. The analyses were carried out using R software, version 4.2.1. Results The total sample consisted of 434 patients who underwent isolated CABG; the mean age was 63 years, with a prevalence of males (71%). Among the patients followed up at the 4-year follow-up (115), 60 (52%) were positive according to the WHO’s definitions. After multiple comparisons, there was a statistical difference in quality of life in all periods (P<0.001). Between patients with and without COVID-19, a statistical difference was observed at 1 and 4 years (p = 0.0039). Conclusion Patients who underwent CABG and had a history of COVID-19 infection experienced worsening quality of life within 4 years. There was no difference between groups regarding new acute myocardial infarction (AMI), stroke, or hospitalization. COVID19 COVID 19 COVID-1 challenge CAD, CAD , (CAD) CABG, (CABG) analyzed 201 enrolled observational crosssectional, crosssectional cross sectional, sectional cross-sectional study (COVID-19 NoCOVID, NoCOVID No (No-COVID) Organizations Organization s WHO (WHO QLCS (QLCS 3 days months year SD. SD . (SD) frequencies score 5 5% software 421 2 4.2.1 43 71%. 71 71% (71%) 4year followup follow 115, 115 (115) 52% 52 (52% WHOs comparisons P<0.001. P0001 P P<0.001 0 001 (P<0.001) COVID19, 19, p 0.0039. 00039 0.0039 0039 0.0039) AMI, AMI (AMI) stroke hospitalization COVID1 COVID- (CAD (CABG 20 (COVID-1 (No-COVID (SD 42 4.2. 7 (71% 11 (115 (52 P000 P<0.00 00 (P<0.001 0003 0.003 003 (AMI (COVID- 4.2 (71 (11 (5 P00 P<0.0 (P<0.00 000 0.00 (COVID 4. (7 (1 ( P0 P<0. (P<0.0 0.0 P<0 (P<0. 0. P< (P<0 (P< (P