ObjectivesTo investigate acute ischemic stroke (AIS) patients with systemic lupus erythematosus (SLE) clinical and imaging features, and to explore the impact of SLE on the short-term prognosis of AIS patients.MethodsA nested case-control study was conducted in The First Affiliated Hospital of Zhengzhou University between October 1, 2019, and May 31, 2021. The case group consisted of 28 AIS patients diagnosed with SLE, and 112 AIS patients without SLE were selected by incidence density sampling as a control group.ResultsAmong 140 patients, the mean age was (48.4 +/- 15.6) years, and 130 (92.9%) were females. Higher levels in low-density lipoprotein cholesterol (LDL-C) (2.5 mmol/L vs. 2.1 mmol/L; P = 0.049), D-dimer (DDi) (0.7 mg/L vs. 0.3 mg/L; P = 0.02), and C-reactive protein (CRP) (13.2 mg/L vs. 6.3 mg/L; P = 0.002) were observed in the case group. On imaging, the case group was more prevalent in simultaneous involvement of the anterior and posterior circulation (42.9% vs. 17.0%; P = 0.004), multiple infarcts (46.4% vs. 20.5%; P = 0.008) and stroke of other undetermined etiologies (SUE) (28.6% vs. 6.3%; P = 0.002) than the control group. SLE (OR 5.94, 95%CI [1.04-34.39]; P = 0.045) was an independent risk factor for a poor short-term prognosis of AIS patients.ConclusionsHigher levels of LDL-C, CRP, and DDi, multiple infarcts and simultaneous involvement of the anterior, and posterior circulation were more prevalent in the AIS patients with SLE. Further, SLE was also found as an independent risk factor for AIS patients' poor short-term prognosis.