BACKGROUND: Early identification of vulnerable plaques at risk of rupture could help prevent cerebral ischemic stroke in patients with carotid artery disease. OBJECTIVE: To investigate the correlation between contrast-enhanced ultrasound (CEUS) perfusion patterns and serum lipid signatures of carotid artery plaques with the degree of carotid stenosis. METHODS: A total of 80 patients with carotid artery plaques who underwent CEUS were included. All patients underwent CEUS, computed tomography angiography or digital subtraction angiography, and serum lipid testing. RESULTS: The contrast agent enhancement levels and the CEUS perfusion patterns in the plaques were associated with the degree of carotid stenosis (P < 0.05). Serum free fatty acid (FFA) was associated with the contrast agent enhancement levels (P 0.05), but did not correlate with the degree of stenosis (P 0.05). There was no significant difference in total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides with respect to contrast agent enhancement levels (P > 0.05) or the degree of stenosis (P > 0.05). CONCLUSION: A high level of CEUS perfusion and increased serum FFA levels are indicative of vulnerable carotid plaques, which may be useful for the prediction of stroke in patients with carotid artery disease.