Objectives The aim of this study was to assess serum lipoprotein profiles using rapid single-spin continuous lipoprotein density profiling (CLPDP) in healthy control cats and cats with hepatic lipidosis (HL). Methods Analysis of serum lipoprotein profiles using the CLPDP was performed in 23 cats with HL and 20 healthy control cats. The area under the curve for each lipoprotein fraction, triglyceride (TG)-rich lipoproteins (TRLs), low-density lipoproteins (LDLs) and high-density lipoproteins (HDLs), was calculated. Serum cholesterol and TG concentrations were measured using a clinical chemistry analyzer. Results Serum cholesterol and TG concentrations were not significantly different between healthy control cats and cats with HL ( P = 0.5075 and P = 0.2541, respectively). LDL content was significantly higher in cats with HL than in healthy control cats ( P = 0.0001), while HDL content was significantly lower in cats with HL than in healthy control cats ( P = 0.0032). TRL content was not significantly different between the two groups ( P = 0.0699). The specific fraction (1.037-1.043 g/ml) within nominal LDL in serum distinguished healthy control cats from cats with HL with a sensitivity of 87% and a specificity of 90%. Conclusions and relevance Serum lipoprotein profiles were altered in cats with HL, even though serum cholesterol and TG concentrations were not significantly different compared with healthy control cats. The CLPDP might be a useful tool for assessing lipid metabolism in cats with HL.