Objectives To help understand the pathogenesis of coronary heart disease (CHD) by doing blood metabonomics comparison on CHD patients with phlegm-turbidity syndrome and without syndrome, and healthy controls. Methods Ninety patients were involved. Among them, 60 patients with CHD were divided into the coronary heart disease with turbid phlegm syndrome group (HZTZ) and the coronary heart disease without turbid phlegm syndrome group (NHZTZ). The additional 30 subjects were the healthy controls (JKZ). The serum endogenous metabolites were determined and analyzed by Liquid chromatography—Mass spectrometry (LC-MS). Results In positive ion mode, there were three identical differential metabolites among the three groups: N2-ethyl-n4-isopropyl-6-(methylthio)-1,3,5-triazine-2,4-diamine, LysoPC (18:2), and methyl palmitate. In negative ion mode, two identical metabolites were identified, which were LysoPC (17:0) and fatty acyl ester of hydroxy fatty acids (FAHFA) (17:1/14:1). These five metabolites of the HZTZ group were higher than those in NHZTZ group and healthy controls. The results identified perturbations in the areas, such as phenylalanine, tyrosine, and tryptophan biosynthesis, starch and sucrose metabolism, carbohydrate digestion and absorption, and so on. Conclusions Metabonomics analysis of serum in patients with CHD with turbid phlegm syndrome uncovered the metabolic disorders of saturated and unsaturated fatty acids in comparison to the patients without turbid phlegm syndrome.