<h3>Background</h3> Although many studies have been conducted within COVID-19, there are still unanswered questions regarding breakthrough infections (BTIs), particularly in patients with systemic lupus erythematosus (SLE). We aimed to determine the occurrence of breakthrough COVID-19 infections in patients with SLE versus other autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs), and healthy controls (HCs). <h3>Methods</h3> The study was based on data from the COVAD questionnaire which amassed a total of 10,783 complete responses from patients with SLE, AIRD, or nrAIRD, and HCs. After exclusion of individuals who were unvaccinated, those who received one vaccine dose only, and those with uncertain responses regarding the vaccine doses, a total of 9,595 patients formed the study population of the present investigation. If a COVID-19 infection occurred after the initial two vaccine doses and at least one booster dose (herein termed full vaccination), it was considered a BTI. Data were analysed using multivariable regression models. <h3>Results</h3> Among SLE patients, 867/1,218 (71.2%) were fully vaccinated. BTI frequencies in fully vaccinated SLE patients were comparable to those of other AIRDs (OR: 1.0; 95% CI: 0.8–1.3; p=0.447) and nrAIDS (OR: 0.9; 95% CI: 0.6–1.3; p=0.856) but higher compared with HCs (OR:1.2; 95% CI: 1.0–1.6; p=0.022). Compared with HCs (OR: 10.6; 95% CI: 1.2–93.0; p=0.032) and other AIRDs (OR: 3.5; 95% CI: 1.08–11.5; p=0.036), SLE patients showed higher frequencies of hospitalisation. <h3>Conclusions</h3> COVID-19 BTIs occurred in nearly 1 every 6th fully vaccinated patient with SLE. Moreover, BTIs in SLE patients were more severe compared with BTIs in HCs or patients with AIRDs other than SLE, resulting in a greater need for hospitalisation. These insights call for greater attention to vaccination in the vulnerable group of SLE patients, with appropriate risk stratification towards optimised vaccination strategies.