There is limited research on the correlation between blood lipid levels and severe ulcerative colitis, and this article helps to reveal the relationship between the two. This study aimed to explore the relationship between blood lipid levels and disease activity, and to evaluate the early predictive value of blood lipid levels for severe ulcerative colitis (UC). Here, we analyzed blood lipid indicators of 210 patients with UC and 210 healthy individuals who visited the hospital between August 2018 and August 2022. We divided the patients with UC into non-severe and severe groups, analyzed the relationship between blood lipid levels and severe UC, and evaluated the early predictive value of blood lipid indicators for severe UC. Compared with healthy individuals, patients with UC had lower total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and non-HDL-C levels (P<0.05). Patients with severe versus non-severe UC had decreased TC, HDL-C, LDL-C, and non-HDL-C levels (P<0.05). The combined detection of TC level and erythrocyte sedimentation rate (ESR) predicted a working characteristic receiver operating characteristic curve area of 0.768 (0.694-0.841) in patients with severe UC, which had good early predictive value with a sensitivity of 77.0% and specificity of 66.7%. TC, HDL-C, LDL-C, and non-HDL-C levels were decreased in patients with severe UC. Combined TC levels and ESRs had good early predictive value for severe UC.